Therapeutic methods employing mutant human interleukin-3 (IL-3) polypeptides

ABSTRACT

The present invention relates to recombinant human interleukin-3 (hIL-3) variant or mutant proteins (muteins). These hIL-3 muteins contain one to three amino acid substitutions and may also have amino acid deletions at both the N- and C- termini. The invention also relates to pharmaceutical compositions containing the hIL-3 muteins and methods for using them. Additionally, the present invention relates to recombinant expression vectors comprising nucleotide sequences encoding the hIL-3 muteins, related microbial expression systems, and processes for making the hIL-3 muteins using the microbial expression systems. Included in the present invention are deletion mutants of hIL-3 in which from 1 to 14 amino acids have been deleted from the N-terminus, and from 1 to 15 amino acids (corresponding to residues 119 to 133) have been deleted from the C-terminus, and which also contain one to three amino acid substitutions in the polypeptide. These hIL-3 mutant polypeptides may have biological activities similar to or better than hIL-3 and, in some cases, may also have an improved side effect profile.

This is a divisional of U.S. Ser. No. 08/411,796, filed Apr. 6, 1995,now U.S. Pat. No. 5,677,149, which was filed as internationalapplication PCT/US93/11198 on Nov. 22, 1993 and which entered the U.S.national stage under 35 U.S.C. § 371 on Apr. 06, 1995; andPCT/US93/11198 is a continuation-in-part of U.S. Ser. No. 07/981,044,filed Nov. 24, 1992 which is now abandoned.

FIELD OF THE INVENTION

The present invention relates to mutants or variants of humaninterleukin-3 (hIL-3) which contain one or more amino acid substitutionsand which may have portions of the native hIL-3 molecule deleted. ThesehIL-3 single and multiple mutation polypeptides retain one or moreactivities of native hIL-3 and may also show improved hematopoieticcell-stimulating activity and/or an improved activity profile which mayinclude reduction of undesirable biological activities associated withnative hIL-3.

BACKGROUND OF THE INVENTION

Colony stimulating factors (CSFs) which stimulate the differentiationand/or proliferation of bone marrow cells have generated much interestbecause of their therapeutic potential for restoring depressed levels ofhematopoietic stem cell-derived cells. CSFs in both human and murinesystems have been identified and distinguished according to theiractivities. For example, granulocyte-CSF (G-CSF) and macrophage-CSF(M-CSF) stimulate the in vitro formation of neutrophilic granulocyte andmacrophage colonies, respectively while GM-CSF and interleukin-3 (IL-3)have broader activities and stimulate the formation of both macrophage,neutrophilic and eosinophilic granulocyte colonies. IL-3 also stimulatesthe formation of mast, megakaryocyte and pure and mixed erythroidcolonies.

Because of its ability to stimulate the proliferation of a number ofdifferent cell types and to support the growth and proliferation ofprogenitor cells, IL-3 has potential for therapeutic use in restoringhematopoietic cells to normal amounts in those cases where the number ofcells has been reduced due to diseases or to therapeutic treatments suchas radiation and chemotherapy.

Interleukin-3 (IL-3) is a hematopoietic growth factor which has theproperty of being able to promote the survival, growth anddifferentiation of hematopoietic cells. Among the biological propertiesof IL-3 are the ability (a) to support the growth and differentiation ofprogenitor cells committed to all, or virtually all, blood celllineages; (b) to interact with early multipotential stem cells; (c) tosustain the growth of pluripotent precursor cells; (d) to stimulateproliferation of chronic myelogenous leukemia (CML) cells; (e) tostimulate proliferation of mast cells, eosinophils and basophils; (f) tostimulate DNA synthesis by human acute myelogenous leukemia (AML) cells;(g) to prime cells for production of leukotrienes and histamines; (h) toinduce leukocyte chemotaxis; and (i) to induce cell surface moleculesneeded for leukocyte adhesion.

Mature human interleukin-3 (hIL-3) consists of 133 amino acids. It hasone disulfide bridge and two potential glycosylation sites (Yang, etal., CELL 47:3 (1986)).

Murine IL-3 (mIL-3) was first identified by Ihle, et al., J. IMMUNOL.126:2184 (1981) as a factor which induced expression of a T cellassociated enzyme, 20-hydroxysteroid dehydrogenase. The factor waspurified to homogeneity and shown to regulate the growth anddifferentiation of numerous subclasses of early hematopoietic andlymphoid progenitor cells.

In 1984, cDNA clones coding for murine IL-3 were isolated (Fung, et al.,NATURE 307:233 (1984) and Yokota, et al., PROC. NATL. ACAD. SCI. USA81:1070 (1984)). The murine DNA sequence coded for a polypeptide of 166amino acids including a putative signal peptide.

The gibbon IL-3 sequence was obtained using a gibbon cDNA expressionlibrary. The gibbon IL-3 sequence was then used as a probe against ahuman genomic library to obtain a human IL-3 sequence.

Gibbon and human genomic DNA homologues of the murine IL-3 sequence weredisclosed by Yang, et al., CELL 47:3 (1986). The human sequence reportedby Yang, et al. included a serine residue at position 8 of the matureprotein sequence. Following this finding, others reported isolation ofPro⁸ hIL-3 cDNAs having proline at position 8 of the protein sequence.Thus it appears that there may be two allelic forms of hIL-3.

Dorssers, et al., GENE 55:115 (1987), found a clone from a human cDNAlibrary which hybridized with mIL-3. This hybridization was the resultof the high degree of homology between the 3' noncoding regions of mIL-3and hIL-3. This cDNA coded for an hIL-3 (Pro⁸) sequence.

U.S. Pat. No. 4,877,729 and U.S. Pat. No. 4,959,455 disclose human IL-3and gibbon IL-3 cDNAs and the protein sequences for which they code. ThehIL-3 disclosed has serine rather than proline at position 8 in theprotein sequence.

Clark-Lewis, et al., SCIENCE 231:134 (1986) performed a functionalanalysis of murine IL-3 analogues synthesized with an automated peptidesynthesizer. The authors concluded that the stable tertiary structure ofthe complete molecule was required for full activity. A study on therole of the disulfide bridges showed that replacement of all fourcysteines by alanine gave a molecule with 1/500th the activity as thenative molecule. Replacement of two of the four Cys residues byAla(Cys⁷⁹, Cys¹⁴⁰ →Ala⁷⁹, Ala¹⁴⁰) resulted in an increased activity. Theauthors concluded that in murine IL-3 a single disulfide bridge isrequired between cysteines 17 and 80 to get biological activity thatapproximates physiological levels and that this structure probablystabilizes the tertiary structure of the protein to give a conformationthat is optimal for function. (Clark-Lewis, et al., PROC. NATL. ACAD.SCI. USA 85:7897 (1988)).

International Patent Application (PCT) WO 88/00598 discloses gibbon- andhuman-like IL-3. The hIL-3 contains a Ser⁸ →Pro⁸ replacement.Suggestions are made to replace Cys by Ser, thereby breaking thedisulfide bridge, and to replace one or more amino acids at theglycosylation sites.

EP-A-0275598 (WO 88/04691) illustrates that Ala¹ can be deleted whileretaining biological activity. Some mutant hIL-3 sequences are provided,e.g., two double mutants, Ala¹ →Asp¹, Trp¹³ →Arg¹³ (pGB/IL-302) and Ala¹→Asp¹, Met³ →Thr³ (pGB/IL-304) and one triple mutant Ala¹ →Asp¹, Leu⁹→Pro⁹, Trp¹³ →Arg¹³ (pGB/IL-303).

WO 88/05469 describes how deglycosylation mutants can be obtained andsuggests mutants of Arg⁵⁴ Arg⁵⁵ and Arg¹⁰⁸ Arg¹⁰⁹ Lys¹¹⁰ might avoidproteolysis upon expression in Saccharomyces cerevisiae by KEX2protease. No mutated proteins are disclosed. Glycosylation and the KEX2protease activity are only important, in this context, upon expressionin yeast.

WO 88/06161 mentions various mutants which theoretically may beconformationally and antigenically neutral. The only actually performedmutations are Met² →Ile² and Ile¹³¹ →Leu¹³¹. It is not disclosed whetherthe contemplated neutralities were obtained for these two mutations.

WO 91/00350 discloses nonglycosylated hIL-3 analog proteins, forexample, hIL-3 (Pro⁸ Asp¹⁵ Asp⁷⁰), Met³ rhul-3 (Pro⁸ Asp¹⁵ Asp⁷⁰); Thr⁴rhuL-3 (Pro⁸ Asp¹⁵ Asp⁷⁰)and Thr⁶ rhuIL-3 (Pro⁸ Asp¹⁵ Asp⁷⁰). It is saidthat these protein compositions do not exhibit certain adverse sideeffects associated with native hIL-3 such as urticaria resulting frominfiltration of mast cells and lymphocytes into the dermis. Thedisclosed analog hIL-3 proteins may have N termini at Met³, Thr⁴, orThr⁶.

WO 90/12874 discloses cysteine added variants (CAVs) of IL-3 which haveat least one Cys residue substituted for a naturally occurring aminoacid residue.

SUMMARY OF THE INVENTION

The present invention relates to recombinant human interleukin-3 (hIL-3)variant or mutant proteins (muteins). These hIL-3 muteins contain aminoacid substitutions and may also have amino acid deletions at either/orboth the N- and C-termini. Preferably, these mutant polypeptides of thepresent invention contain one to three amino acids which differ from theamino acids found at the corresponding positions in the native hIL-3polypeptide. The invention also relates to pharmaceutical compositionscontaining the hIL-3 muteins, DNA coding for the muteins, and methodsfor using the muteins. Additionally, the present invention relates torecombinant expression vectors comprising nucleotide sequences encodingthe hIL-3 muteins, related microbial expression systems, and processesfor making the hIL-3 muteins using the microbial expression systems.

The present invention includes mutants of hIL-3 in which from 1 to 14amino acids have been deleted from the N-terminus and/or from 1 to 15amino acids have been deleted from the C-terminus, and in which from oneto three amino acid substitutions have been made. Preferred muteins ofthe present invention are those in which amino acids 1 to 14 have beendeleted from the N-terminus, or amino acids 126 to 133 have been deletedfrom the C-terminus, and which both also contain from one to three aminoacid substitutions in the polypeptide sequence. These hIL-3 multiplemutation polypeptides may have biological activities similar to orbetter than hIL-3 and, in some cases, may also have an improved sideeffect profile, i.e., some muteins may have a better therapeutic indexthan native hIL-3. The present invention also provides muteins which mayfunction as IL-3 antagonists or as discrete antigenic fragments for theproduction of antibodies useful in immunoassay and immunotherapyprotocols. In addition to the use of the hIL-3 mutant polypeptides ofthe present invention in vivo, it is envisioned that in vitro uses wouldinclude the ability to stimulate bone marrow and blood cell activationand growth before infusion into patients.

Antagonists of hIL-3 would be particularly useful in blocking the growthof certain cancer cells like AML, CML and certain types of B lymphoidcancers. Other conditions where antagonists would be useful includethose in which certain blood cells are produced at abnormally highnumbers or are being activated by endogenous ligands. Antagonists wouldeffectively compete for ligands, presumably naturally occurringhemopoietins including and not limited to IL-3, GM-CSF and IL-5, whichmight trigger or augment the growth of cancer cells by virtue of theirability to bind to the IL-3 receptor complex while intrinsic activationproperties of the ligand are diminished. IL-3, GM-CSF and or IL-5 alsoplay a role in certain asthmatic responses. An antagonist of the IL-3receptor may have utility in this disease by blocking receptor-mediatedactivation and recruitment of inflammatory cells.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is the human IL-3 gene for E. coli expression (pMON5873),encoding the polypeptide sequence of natural (wild type) human IL-3 [SEQID NO:128], plus an initiator methionine, as expressed in E. coli, withthe amino acids numbered from the N-terminus of the natural hIL-3.

FIG. 2: ClaI to NsiI Replacement Fragment. FIG. 2 shows the nucleotidesequence of the replacement fragment used between the ClaI and NsiIsites of the hIL-3 gene. The codon choice used in the fragmentcorresponds to that found in highly expressed E. coli genes (Gouy andGautier, 1982). Three new unique restriction sites, EcoRV, XhoI and PstIwere introduced for the purpose of inserting synthetic gene fragments.The portion of the coding sequence shown encodes hIL-3 amino acids20-70.

FIGS. 3 and 4 show the nucleotide and amino acid sequence of the gene inpMON5873 with the sequence extending from NcoI through HindIII. Thecodon choices used to encode amino acids 1-14 and 107-133 correspond tothat found in highly expressed E. coli genes.

FIG. 5 shows the construction of the plasmid vector pMON5846 whichencodes [Met-(1-133) hIL-3 (Arg¹²⁹)].

FIG. 6 shows the construction of the plasmid vector pMON5847 (ATCC68912) which encodes [Met-(1-133) IL-3 (Arg¹²⁹)].

FIG. 7 shows the construction of plasmid vector pMON5853 which encodes[Met-(15-133) hIL-3 (Arg¹²⁹)].

FIG. 8 shows the construction of the plasmid vector pMON5854 whichencodes [Met-(1-133) hIL-3 (Arg¹²⁹)].

FIG. 9 shows the DNA sequence and resulting amino acid sequence of thelamB signal peptide.

FIG. 10 shows the construction of the plasmid vector pMON5978 whichencodes Met-Ala-(15-125)hIL-3.

FIG. 11 shows the construction of the plasmid vector pMON5988 whichencodes Met-Ala(15-125)hIL-3.

FIG. 12 shows the construction of the plasmid vector pMON5887 whichencodes Met-(1-125)hIL-3.

FIG. 13 shows the construction of pMON6457 which encodes (15-125)hIL-3;it contains the araBAD promoter and the lamB signal peptide fused to thevariant hIL-3 amino acids 15-125.

FIG. 14 shows the construction of pMON6458; it contains the araBADpromoter and the lamB signal peptide fused to the variant hIL-3 aminoacids 15-125.

FIG. 15 shows the construction of pMON6467 in which the bases encodingamino acids 35-40 of hIL-3 were deleted using site-directed PCRmutagenesis methods. pMON6467 was used as the template for thegeneration of single amino acid variants at positions 35-40 of hIL-3.

FIG. 16 shows the construction of single amino acid substitutions atposition 35 of hIL-3 using site-directed PCR mutagenesis methods. Themutagenesis results in 20 different single amino substitutions, which isreferred to as a "library", at position 35 of hIL-3.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to muteins of human interleukin-3 (hIL-3)in which amino acid substitutions have been made at from one to threepositions in the amino acid sequence of the polypeptide and to hIL-3muteins which have substantially the same structure and substantiallythe same biological activity. Preferred muteins of the present inventionare (15-125)hIL-3 deletion mutants which have deletions of amino acids 1to 14 at the N-terminus and/or 126 to 133 at the C-terminus and whichboth also have from one to three amino acid substitutions in thepolypeptide and muteins having substantially the same structure andsubstantially the same biological activity. As used herein humaninterleukin-3 corresponds to the amino acid sequence (1-133) as depictedin FIG. 1 and (15-125) hIL-3 corresponds to the 15 to 125 amino acidsequence of the hIL-3 polypeptide. Naturally occurring variants of hIL-3polypeptide amino acids are also included in the present invention (forexample, the allele in which proline rather than serine is at position 8in the hIL-3 polypeptide sequence) as are variant hIL-3 molecules whichare modified post-translationally (e.g. glycosylation).

The present invention also includes the DNA sequences which code for themutant polypeptides, DNA sequences which are substantially similar andperform substantially the same function, and DNA sequences which differfrom the DNAs encoding the muteins of the invention only due to thedegeneracy of the genetic code.

Included in the present invention are novel mutant human interleukin-3polypeptides comprising a polypeptide having the amino acid sequence ofnative human interleukin-3 wherein amino acids 126 to 133 have beendeleted from the C-terminus of the native human interleukin-3polypeptide and amino acids 1 to 14 have been deleted from theN-terminus of the native human interleukin-3 polypeptide and, inaddition, polypeptides of the present invention also have one to threeamino acid substitutions in the polypeptide sequence. The muteins of thepresent invention can have from one to three amino acid substitutions inthe hIL-3 polypeptide chain and, in addition, can have deletions ofamino acids at the N-terminus and/or the C-terminus.

Also included in the present invention are the DNA sequences coding forthe muteins of the present invention; the oligonucleotide intermediatesused to construct the mutant DNAs; and the polypeptides coded for bythese oligonucleotides. These polypeptides may be useful as antagonistsor as antigenic fragments for the production of antibodies useful inimmunoassay and immunotherapy protocols.

The mutant hIL-3 polypeptides of the present invention may also havemethionine, alanine, or methionine-alanine residues inserted at theN-terminus.

The present invention includes hIL-3 mutant polypeptides of the formulaI:

    Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn                                                       [SEQ ID NO:15]                               1               5                   10                  15                    - Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa                                 20                  25                  30                    - Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa                                 35                  40                  45                    - Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa                                 50                  55                  60                    - Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa                                 65                  70                  75                    - Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa                                 80                  85                  90                    - Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa                                 95                 100                 105                    - Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa                                110                 115                 120                    - Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe                                        125                 130                                 

wherein

Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;

Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;

Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;

Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;

Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr,Ser or Val;

Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu,Val or Gly;

Xaa at position 23 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, orArg;

Xaa at position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;

Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;

Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp;

Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;

Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;

Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val;

Xaa at position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;

Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;

Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;

Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu;

Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala,Phe, Ile or Met;

Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;

Xaa at position 36 is Asp, Leu, or Val;

Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;

Xaa at position 38 is Asn, or Ala;

Xaa at position 40 is Leu, Trp, or Arg;

Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met, or Pro;

Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu,Phe, Tyr, Ile, Met or Ala;

Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg,Thr, Gly or Ser;

Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn,Gln, Ala or Pro;

Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp,Asn, Arg, Ser, Ala, Ile, Glu or His;

Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His,Ala, Tyr, Ile, Val or Gly;

Xaa at position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His;

Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr,Ala, Met, Val or Asn;

Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;

Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile,Val, His, Phe, Met or Gln;

Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;

Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;

Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;

Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His,Ala or Leu;

Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;

Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala,Tyr, Phe, Leu, Val or Lys;

Xaa at position 57 is Asn or Gly;

Xaa at position 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;

Xaa at position 59 is Glu Tyr, His, Leu, Pro, or Arg;

Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr;

Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;

Xaa at position 62 is Asn His, Val, Arg, Pro, Thr, Asp, or Ile;

Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;

Xaa at position 64 is Ala, Asn, Pro, Ser, or Lys;

Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;

Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;

Xaa at position 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;

Xaa at position 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;

Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;

Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;

Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, orAsn;

Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;

Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;

Xaa at position 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala;

Xaa at position 75 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, orLeu;

Xaa at position 76 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;

Xaa at position 77 is Ile, Ser, Arg, Thr, or Leu;

Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;

Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;

Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;

Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;

Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr,Ser, Ala, Tyr, Phe, Ile, Met or Val;

Xaa at position 83 is Pro, Ala, Thr, Trp, Arg, or Met;

Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;

Xaa at position 85 is Leu, Asn, Val, or Gln;

Xaa at position 86 is Pro, Cys, Arg, Ala, or Lys;

Xaa at position 87 is Leu, Ser, Trp, or Gly;

Xaa at position 88 is Ala, Lys, Arg, Val, or Trp;

Xaa at position 89 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;

Xaa at position 90 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;

Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;

Xaa at position 92 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile orLeu;

Xaa at position 93 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;

Xaa at position 94 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Ala,or Pro;

Xaa at position 95 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys,Ser, Ala, Trp, Phe, Ile, or Tyr;

Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr;

Xaa at position 97 is Ile, Val, Lys, Ala, or Asn;

Xaa at position 98 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser,Phe, Met, Val, Lys, Arg, Tyr or Pro;

Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe,or His;

Xaa at position 100 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro;

Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn,Ser, Ala, Gly, Ile, Leu, or Gln;

Xaa at position 102 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;

Xaa at position 103 is Asp, or Ser;

Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys,Ala, Phe, or Gly;

Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys,Ile, Asp, or His;

Xaa at position 106 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;

Xaa at position 108 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Alaor Pro;

Xaa at position 109 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;

Xaa at position 110 is Lys, Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser,or Trp;

Xaa at position 111 is Leu, Ile, Arg, Asp, or Met;

Xaa at position 112 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;

Xaa at position 113 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu,Ile, Val or Asn;

Xaa at position 114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;

Xaa at position 115 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, orMet;

Xaa at position 116 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp,Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile;

Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;

Xaa at position 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;

Xaa at position 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;

Xaa at position 120 is Asn, Ala, Pro, Leu, His, Val, or Gln;

Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;

Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr,or Cys;

Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;

and which can additionally have Met- preceding the amino acid inposition 1; and wherein from 1 to 14 amino acids can be deleted from theN-terminus and/or from 1 to 15 amino acids can be deleted from theC-terminus; and wherein from one to three of the amino acids designatedby Xaa are different from the corresponding amino acids of native(1-133) human interleukin-3 with the proviso that when Xaa at position22 is Leu, and/or Xaa at position 34 is Gly or Glu, and/or Xaa atposition 44 is Ala, and/or Xaa at position 46 is Lys or Ala, and/or Xaaat position 50 is Lys, and/or Xaa at position 59 is Pro or Arg, and/orXaa at position 63 is Lys, and/or Xaa at position 75 is Gly or Arg,and/or Xaa at position 94 is Pro, and/or Xaa at position 98 is Arg,and/or Xaa at position 106 is Lys, and/or Xaa at position 110 is Ala orGlu, and/or Xaa at position 111 is Met, then there must be at least oneadditional substitution besides the ones indicated.

Included in the present invention are (1-133)hIL-3 mutant polypeptidesof the Formula II:

    Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn                                                       [SEQ ID NO:16]                               1               5                   10                  15                    - Cys Xaa Xaa Xaa Xaa Xaa Glu Xaa Xaa Xaa Xaa Leu Xaa Xaa Xaa                                 20                  25                  30                    - Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Leu Xaa Xaa Glu Xaa Xaa                                 35                  40                  45                    - Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Leu Xaa Xaa                                 50                  55                  60                    - Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa                                 65                  70                  75                    - Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Cys Xaa Pro Xaa Xaa Xaa Xaa                                 80                  85                  90                    - Xaa Xaa Xaa Arg Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asp Xaa Xaa                                 95                 100                 105                    - Xaa Phe Xaa Xaa Lys Leu Xaa Phe Xaa Xaa Xaa Xaa Leu Xaa Xaa                                110                 115                 120                    - Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe                                        125                 130                                 

wherein

Xaa at position 17 is Ser, Gly, Asp, Met, or Gln;

Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln;

Xaa at position 19 is Met, Phe, Ile, Arg, or Ala;

Xaa at position 20 is Ile or Pro;

Xaa at position 21 is Asp or Glu;

Xaa at position 23 is Ile, Val, Ala, Leu, or Gly;

Xaa at position 24 is Ile, Val, Phe, or Leu;

Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;

Xaa at position 26 is His, Phe, Gly, Arg, or Ala;

Xaa at position 28 is Lys, Leu, Gln, Gly, Pro, or Val;

Xaa at position 29 is Gln, Asn, Leu, Arg, or Val;

Xaa at position 30 is Pro, His, Thr, Gly, or Gln;

Xaa at position 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;

Xaa at position 32 is Leu, Arg, Gln, Asn, Gly, Ala, or Glu;

Xaa at position 33 is Pro, Leu, Gln, Ala, or Glu;

Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Ala, Arg, Gln, Glu, Ile,Phe, Thr or Met;

Xaa at position 35 is Leu, Ala, Asn, Pro, Gln, or Val;

Xaa at position 36 is Asp or Leu;

Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile;

Xaa at position 38 is Asn or Ala;

Xaa at position 41 is Asn, Cys, Arg, His, Met, or Pro;

Xaa at position 42 is Gly, Asp, Ser, Cys, Ala, Asn, Ile, Leu, Met, Tyr,Val or Arg;

Xaa at position 44 is Asp or Glu;

Xaa at position 45 is Gln, Val, Met, Leu, Thr, Lys, Ala, Asn, Glu, Ser,or Trp;

Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Ala, Asn, Gln, Glu, His,Ile, Lys, Tyr, Val or Gly;

Xaa at position 47 is Ile, Val, or His;

Xaa at position 49 is Met, Asn, or Asp;

Xaa at position 50 is Glu, Thr, Ala, Asn, Ser or Asp;

Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;

Xaa at position 52 is Asn or Gly;

Xaa at position 53 is Leu, Met, or Phe;

Xaa at position 54 is Arg, Ala, or Ser;

Xaa at position 55 is Arg, Thr, Val, Leu, or Gly;

Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Ala, Arg, Asn, Glu, His,Leu, Thr, Val or Lys;

Xaa at position 59 is Glu, Tyr, His, Leu, or Arg;

Xaa at position 60 is Ala, Ser, Asn, or Thr;

Xaa at position 61 is Phe or Ser;

Xaa at position 62 is Asn, Val, Pro, Thr, or Ile;

Xaa at position 63 is Arg, Tyr, Lys, Ser, His, or Val;

Xaa at position 64 is Ala or Asn;

Xaa at position 65 is Val, Thr, Leu, or Ser;

Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;

Xaa at position 67 is Ser, Phe, Val, Gly, Asn, Ile, or His;

Xaa at position 68 is Leu, Val, Ile, Phe, or His;

Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, or Gly;

Xaa at position 70 is Asn or Pro;

Xaa at position 71 is Ala, Met, Pro, Arg, Glu, Thr, or Gln;

Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;

Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, Arg, or Pro;

Xaa at position 74 is Ile or Met;

Xaa at position 75 is Glu, Gly, Asp, Ser, or Gln;

Xaa at position 76 is Ser, Val, Ala, Asn, Glu, Pro, Gly, or Asp;

Xaa at position 77 is Ile, Ser, or Leu;

Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;

Xaa at position 80 is Asn, Val, Gly, Thr, Leu, Glu, or Arg;

Xaa at position 81 is Leu, or Val;

Xaa at position 82 is Leu, Gln, Trp, Arg, Asp, Ala, Asn, Glu, His, Met,Phe, Ser, Thr, Tyr or Val;

Xaa at position 83 is Pro, Ala, Thr, Trp, or Met;

Xaa at position 85 is Leu or Val;

Xaa at position 87 is Leu or Ser;

Xaa at position 88 is Ala, Arg, or Trp;

Xaa at position 89 is Thr, Asp, Glu, His, Asn, or Ser;

Xaa at position 90 is Ala, Asp, or Met;

Xaa at position 91 is Ala, Pro, Ser, Thr, Phe, Leu, or Asp;

Xaa at position 92 is Pro or Ser;

Xaa at position 93 is Thr, Asp, Ser, Pro, Ala, Leu, or Arg;

Xaa at position 95 is His, Pro, Arg, Val, Leu, Gly, Asn, Ile, Phe, Seror Thr;

Xaa at position 96 is Pro or Tyr;

Xaa at position 97 is Ile, Val, or Ala;

Xaa at position 98 is His, Ile, Asn, Asp, Ala, Thr, Leu, Arg, Gln, Glu,lys, Met, Ser, Tyr, Val or Pro;

Xaa at position 99 is Ile, Leu, Val, or Phe;

Xaa at position 100 is Lys, Leu, His, Arg, Ile, Gln, Pro, or Ser;

Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Val, Asn, Ile, Leuor Tyr;

Xaa at position 102 is Gly, Glu, Lys, or Ser;

Xaa at position 104 is Trp, Val, Tyr, Met, or Leu;

Xaa at position 105 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys,Ile, Asp, or His;

Xaa at position 106 is Glu, Ser, Ala, or Gly;

Xaa at position 108 is Arg, Ala, Gln, Ser or Lys;

Xaa at position 109 is Arg, Thr, Glu, Leu, Ser, or Gly;

Xaa at position 112 is Thr, Val, Gln, Glu, His, or Ser;

Xaa at position 114 is Tyr or Trp;

Xaa at position 115 is Leu or Ala;

Xaa at position 116 is Lys, Thr, Met, Val, Trp, Ser, Leu, Ala, Asn, Gln,His, Met, Phe, Tyr or Ile;

Xaa at position 117 is Thr, Ser, or Asn;

Xaa at position 119 is Glu, Ser, Pro, Leu, Thr, or Tyr;

Xaa at position 120 is Asn, Pro, Leu, His, Val, or Gln;

Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;

Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr,or Cys;

Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;

and which can additionally have Met- preceding the amino acid inposition 1; and wherein from 1 to 14 amino acids can be deleted from theN-terminus and/or from 1 to 15 amino acids can be deleted from theC-terminus; and wherein from one to three of the amino acids designatedby Xaa are different from the corresponding amino acids of native(1-133) human interleukin-3 with the proviso that when Xaa at position34 is Gly or/and Xaa or position 46 is Lys or Ala or/and Xaa at position59 is Arg and/or Xaa at position 63 is Lys and/or Xaa at position 75 isGly and/or Xaa at position 98 is Arg then there must be at least oneadditional substitution besides the ones indicated.

Included in the present invention are (1-133)hIL-3 mutant polypeptidesof the Formula III:

    Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn                                                       [SEQ ID NO:17]                               1               5                   10                  15                    - Cys Xaa Xaa Xaa Ile Xaa Glu Xaa Xaa Xaa Xaa Leu Lys Xaa Xaa                                 20                  25                  30                    - Xaa Xaa Xaa Xaa Xaa Asp Xaa Xaa Asn Leu Asn Xaa Glu Xaa Xaa                                 35                  40                  45                    - Xaa Ile Leu Met Xaa Xaa Asn Leu Xaa Xaa Xaa Asn Leu Glu Xaa                                 50                  55                  60                    - Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Ile Glu                                 65                  70                  75                    - Xaa Xaa Leu Xaa Xaa Leu Xaa Xaa Cys Xaa Pro Xaa Xaa Thr Ala                                 80                  85                  90                    - Xaa Pro Xaa Arg Xaa Xaa Xaa Xaa Xaa Xaa Xaa Gly Asp Xaa Xaa                                 95                 100                 105                    - Xaa Phe Xaa Xaa Lys Leu Xaa Phe Xaa Xaa Xaa Xaa Leu Glu Xaa                                110                 115                 120                    - Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe                                        125                 130                                 

wherein

Xaa at position 17 is Ser, Gly, Asp, Met, or Gln;

Xaa at position 18 is Asn, His, or Ile;

Xaa at position 19 is Mot or Ile;

Xaa at position 21 is Asp or Glu;

Xaa at position 23 is Ile, Ala, Leu, or Gly;

Xaa at position 24 is Ile, Val, or Leu;

Xaa at position 25 is Thr, His, Gln, or Ala;

Xaa at position 26 is His or Ala;

Xaa at position 29 is Gln, Asn, or Val;

Xaa at position 30 is Pro, Gly, or Gln;

Xaa at position 31 is Pro, Asp, Gly, or Gln;

Xaa at position 32 is Leu, Arg, Gln, Asn, Gly, Ala, or Glu;

Xaa at position 33 is Pro or Glu;

Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Ala, Arg, Gln, Glu, Ile,Phe, Thr or Met;

Xaa at position 35 is Leu, Ala, Asn, Pro, Gln, or Val;

Xaa at position 37 is Phe, Ser, Pro, or Trp;

Xaa at position 38 is Asn or Ala;

Xaa at position 42 is Gly, Asp, Ser, Cys, Ala, Asn, Ile, Leu, Met, Tyror Arg;

Xaa at position 44 is Asp or Glu;

Xaa at position 45 is Gln, Val, Met, Leu, Thr, Ala, Asn, Glu, Ser orLys;

Xaa at position 46 is Asp, Phe, Ser, Thr, Ala, Asn Gln, Glu, His, Ile,Lys, Tyr, Val or Cys;

Xaa at position 50 is Glu, Ala, Asn, Ser or Asp;

Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His;

Xaa at position 54 is Arg or Ala;

Xaa at position 54 is Arg or Ala;

Xaa at position 55 is Arg, Thr, Val, Leu, or Gly;

Xaa at position 56 is Pro, Gly, Ser, Gln, Ala, Arg, Asn, Glu, Leu, Thr,Val or Lys;

Xaa at position 60 is Ala or Ser;

Xaa at position 62 is Asn, Pro, Thr, or Ile;

Xaa at position 63 is Arg or Lys;

Xaa at position 64 is Ala or Asn;

Xaa at position 65 is Val or Thr;

Xaa at position 66 is Lys or Arg;

Xaa at position 67 is Ser, Phe, or His;

Xaa at position 68 is Leu, Ile, Phe, or His;

Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, or Gly;

Xaa at position 71 is Ala, Pro, or Arg;

Xaa at position 72 is Ser, Glu, Arg, or Asp;

Xaa at position 73 is Ala or Leu;

Xaa at position 76 is Ser, Val, Ala, Asn, Glu, Pro, or Gly;

Xaa at position 77 is Ile or Leu;

Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;

Xaa at position 80 is Asn, Gly, Glu, or Arg;

Xaa at position 82 is Leu, Gln, Trp, Arg, Asp, Ala, Asn, Glu, His, Ile,Met, Phe, Ser, Thr, Tyr or Val;

Xaa at position 83 is Pro or Thr;

Xaa at position 85 is Leu or Val;

Xaa at position 87 is Leu or Ser;

Xaa at position 88 is Ala or Trp;

Xaa at position 91 is Ala or Pro;

Xaa at position 93 is Thr, Asp, Ser, Pro, Ala, Leu, or Arg;

Xaa at position 95 is His, Pro, Arg, Val, Leu, Gly, Asn, Phe, Ser orThr;

Xaa at position 96 is Pro or Tyr;

Xaa at position 97 is Ile or Val;

Xaa at position 98 is His, Ile, Asn, Leu, Ala, Thr, Arg, Gln, Leu, Lys,Met, Ser, Tyr, Val or Pro;

Xaa at position 99 is Ile, Leu, or Val;

Xaa at position 100 is Lys, Arg, Ile, Gln, Pro, or Ser;

Xaa at position 101 is Asp, Pro, Met, Lys, His, Thr, Pro, Asn, Ile, Leuor Tyr;

Xaa at position 104 is Trp or Leu;

Xaa at position 105 is Asn, Pro, Ala, Ser, Trp, Gln, Tyr, Leu, Lys, Ile,Asp, or His;

Xaa at position 106 is Glu or Gly;

Xaa at position 108 is Arg, Ala, or Ser;

Xaa at position 109 is Arg, Thr, Glu, Leu, or Ser;

Xaa at position 112 is Thr, Val, or Gln;

Xaa at position 114 is Tyr or Trp;

Xaa at position 115 is Leu or Ala;

Xaa at position 116 is Lys, Thr, Val, Trp, Ser, Ala, His, Met, Phe, Tyror Ile;

Xaa at position 117 is Thr or Ser;

Xaa at position 120 is Asn, Pro, Leu, His, Val, or Gln;

Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Asp, or Gly;

Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr,or Cys;

Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;

and which can additionally have Met- preceding the amino acid inposition 1; and wherein from 1 to 14 amino acids can be deleted from theN-terminus and/or from 1 to 15 amino acids can be deleted from theC-terminus; and wherein from one to three of the amino acids designatedby Xaa are different from the corresponding amino acids of native(1-133) human interleukin-3 with the proviso that when Xaa at position22 is Leu, and/or Xaa at position 34 is Gly or Glu, and/or Xaa atposition 44 is Ala, and/or Xaa at position 46 is Lys or Ala, and/or Xaaat position 50 is Lys, and/or Xaa at position 59 is Pro or Arg, and/orXaa at position 63 is Lys, and/or Xaa at position 75 is Gly or Arg,and/or Xaa at position 94 is Pro, and/or Xaa at position 98 is Arg,and/or Xaa at position 106 is Lys, and/or Xaa at position 110 is Ala orGlu, and/or Xaa at position 111 is Met, then there must be at least oneadditional substitution besides the ones indicated, and which canadditionally have Met- preceding the amino acid in position 1; andwherein from 1 to 14 amino acids can be deleted from the N-terminusand/or from 1 to 15 amino acids can be deleted from the C-terminus; andwherein from one to three of the amino acids designated by Xaa aredifferent from the corresponding amino acids of native (1-133)humaninterleukin-3 with the proviso that when Xaa at position 34 is Glyand/or Xaa at position 46 is Lys or Ala, and/or Xaa at position 63 isLys, and/or Xaa at position 98 is Arg, then two or three of the aminoacid designated by Xaa are different from the corresponding amino acidsof the native (1-133) human interleukin-3.

Included in the present invention are (1-133)hIL-3 mutant polypeptidesof the Formula IV:

    Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn                                                      [SEQ ID NO:18]                                1               5                   10                  15                    - Cys Xaa Xaa Met Ile Asp Glu Xaa Ile Xaa Xaa Leu Lys Xaa Xaa                                 20                  25                  30                    - Pro Xaa Pro Xaa Xaa Asp Phe Xaa Asn Leu Asn Xaa Glu Asp Xaa                                 35                  40                  45                    - Xaa Ile Leu Met Xaa Xaa Asn Leu Arg Xaa Xaa Asn Leu Glu Ala                                 50                  55                  60                    - Phe Xaa Arg Xaa Xaa Lys Xaa Xaa Xaa Asn Ala Ser Ala Ile Glu                                 65                  70                  75                    - Xaa Xaa Leu Xaa Xaa Leu Xaa Pro Cys Leu Pro Xaa Xaa Thr Ala                                 80                  85                  90                    - Xaa Pro Xaa Arg Xaa Pro Ile Xaa Xaa Xaa Xaa Gly Asp Trp Xaa                                 95                 100                 105                    - Glu Phe Xaa Xaa Lys Leu Xaa Phe Tyr Leu Xaa Xaa Leu Glu Xaa                                110                 115                 120                    - Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe                                        125                 130                                 

wherein

Xaa at position 17 is Ser, Gly, Asp, or Gln;

Xaa at position 18 is Asn, His, or Ile;

Xaa at position 23 is Ile, Ala, Leu, or Gly;

Xaa at position 25 is Thr, His, or Gln;

Xaa at position 26 is His or Ala;

Xaa at position 29 is Gln or Asn;

Xaa at position 30 is Pro or Gly;

Xaa at position 32 is Leu, Arg, Asn, or Ala;

Xaa at position 34 is Leu, Val, Ser, Ala, Arg, Gln, Glu, Ile, Phe, Thr,or Met;

Xaa at position 35 is Leu, Ala, Asn, or Pro;

Xaa at position 38 is Asn or Ala;

Xaa at position 42 is Gly, Asp, Ser, Ala, Asn, Ile, Leu, Met, Tyr orArg;

Xaa at position 45 is Gln, Val, Met, Leu, Ala, Asn, Glu, or Lys;

Xaa at position 46 is Asp, Phe, Ser, Ala, Gln, Glu, His, Val or Thr;

Xaa at position 50 is Glu Asn, Ser or Asp;

Xaa at position 51 is Asn, Arg, Pro, Thr, or His;

Xaa at position 55 is Arg, Leu, or Gly;

Xaa at position 56 is Pro, Gly, Ser, Ala, Asn, Val, Leu or Gln;

Xaa at position 62 is Asn, Pro, or Thr;

Xaa at position 64 is Ala or Asn;

Xaa at position 65 is Val or Thr;

Xaa at position 67 is Ser or Phe;

Xaa at position 68 is Leu or Phe;

Xaa at position 69 is Gln, Ala, Glu, or Arg;

Xaa at position 76 is Ser, Val, Asn, Pro, or Gly;

Xaa at position 77 is Ile or Leu;

Xaa at position 79 is Lys, Asn, Met, Arg, Ile, or Gly;

Xaa at position 80 is Asn, Gly, Glu, or Arg;

Xaa at position 82 is Leu, Gln, Trp, Arg, Asp, Asn, Glu, His, Met, Phe,Ser, Thr, Tyr or Val;

Xaa at position 87 is Leu or Ser;

Xaa at position 88 is Ala or Trp;

Xaa at position 91 is Ala or Pro;

Xaa at position 93 is Thr, Asp, or Ala;

Xaa at position 95 is His, Pro, Arg, Val, Gly, Asn, Ser or Thr;

Xaa at position 98 is His, Ile, Asn, Ala, Thr, Arg, Gln, Glu, Lys, Met,Ser, Tyr, Val or Leu;

Xaa at position 99 is Ile or Leu;

Xaa at position 100 is Lys or Arg;

Xaa at position 101 is Asp, Pro, Met, Lys, Thr, His, Pro, Asn, Ile, Leuor Tyr;

Xaa at position 105 is Asn, Pro, Ser, Ile or Asp;

Xaa at position 108 is Arg, Ala, or Ser;

Xaa at position 109 is Arg, Thr, Glu, Leu, or Ser;

Xaa at position 112 is Thr or Gln;

Xaa at position 116 is Lys, Val, Trp, Ala, His, Phe, Tyr or Ile;

Xaa at position 117 is Thr or Ser;

Xaa at position 120 is Asn, Pro, Leu, His, Val, or Gln;

Xaa at position 121 is Ala, Ser, Ile, Pro, or Asp;

Xaa at position 122 is Gln, Met, Trp, Phe, Pro, His, Ile, or Tyr;

Xaa at position 123 is Ala, Met, Glu, Ser, or Leu;

and which can additionally have Met- preceding the amino acid inposition 1; and wherein from 1 to 14 amino acids can be deleted from theN-terminus and/or from 1 to 15 amino acids can be deleted from theC-terminus; and wherein from one to three of the amino acids designatedby Xaa are different from the corresponding amino acids of native(1-133)human interleukin-3.

Preferred polypeptides of the present invention are (15-125)hIL-3 mutantpolypeptides of the Formula V:

    Asn Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa                                                       [SEQ ID NO:19]                              1                5                   10                 15                     - Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa                                 20                  25                  30                    - Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa                                 35                  40                  45                    - Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa                                 50                  55                  60                    - Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa                                 65                  70                  75                    - Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa                                 80                  85                  90                    - Xaa Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa                                 95                 100                 105                    - Xaa Xaa Xaa Xaa Gln Gln                                                                    110                                                     

wherein

Xaa at position 3 is Ser, Lys, Gly, Asp, Met, Gln, or Arg;

Xaa at position 4 is Asn, His, Leu, Ile, Phe, Arg, or Gln;

Xaa at position 5 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;

Xaa at position 6 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala;

Xaa at position 7 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr,Ser or Val;

Xaa at position 8 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu,Val, or Gly;

Xaa at position 9 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, orArg;

Xaa at position 10 is Ile, Gly, Val, Arg, Ser, Phe, or Leu;

Xaa at position 11 is Thr, His, Gly, Gln, Arg, Pro, or Ala;

Xaa at position 12 is His, Thr, Phe, Gly, Arg, Ala, or Trp;

Xaa at position 13 is Leu, Gly, Arg, Thr, Ser, or Ala;

Xaa at position 14 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp;

Xaa at position 15 is Gln, Asn, Leu, Pro, Arg, or Val;

Xaa at position 16 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys;

Xaa at position 17 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;

Xaa at position 18 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu;

Xaa at position 19 is Pro, Leu, Gln, Ala, Thr, or Glu;

Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala,Phe, Ile or Met;

Xaa at position 21 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;

Xaa at position 22 is Asp, Leu, or Val;

Xaa at position 23 is Phe, Ser, Pro, Trp, or Ile;

Xaa at position 24 is Asn, or Ala;

Xaa at position 26 is Leu, Trp, or Arg;

Xaa at position 27 is Asn, Cys, Arg, Leu, His, Met, Pro;

Xaa at position 28 is Gly, Asp, Ser, Cys, Ala, Lys, Asn, Thr, Leu, Val,Glu, Phe, Tyr, Ile or Met;

Xaa at position 29 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg,Thr, Gly or Ser;

Xaa at position 30 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn,Gln, Ala or Pro;

Xaa at position 31 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Asp, Asn,Arg, Ser, Ala, Ile, Glu, His or Trp;

Xaa at position 32 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His,Ala, Tyr, Ile, Val or Gly;

Xaa at position 33 is Ile, Gly, Val, Ser, Arg, Pro, or His;

Xaa at position 34 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr,Ala, Met, Val or Asn;

Xaa at position 35 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;

Xaa at position 36 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile,Val, His, Phe, Met or Gln;

Xaa at position 37 is Asn, Arg, Met, Pro, Ser, Thr, or His;

Xaa at position 38 is Asn, His, Arg, Leu, Gly, Ser, or Thr;

Xaa at position 39 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, Met, or;

Xaa at position 40 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His,Ala or Leu;

Xaa at position 41 is Arg, Thr, Val, Ser, Leu, or Gly;

Xaa at position 42 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala,Tyr, Phe, Leu, Val or Lys;

Xaa at position 43 is Asn or Gly;

Xaa at position 44 is Leu, Ser, Asp, Arg, Gln, Val, or Cys;

Xaa at position 45 is Glu Tyr, His, Leu, Pro, or Arg;

Xaa at position 46 is Ala, Ser, Pro, Tyr, Asn, or Thr;

Xaa at position 47 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;

Xaa at position 48 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;

Xaa at position 49 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val;

Xaa at position 50 is Ala, Asn, Pro, Ser, or Lys;

Xaa at position 51 is Val, Thr, Pro, His, Leu, Phe, or Ser;

Xaa at position 52 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;

Xaa at position 53 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;

Xaa at position 54 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His;

Xaa at position 55 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu;

Xaa at position 56 is Asn, Leu, Val, Trp, Pro, or Ala;

Xaa at position 57 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, orAsn;

Xaa at position 58 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;

Xaa at position 59 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg;

Xaa at position 60 is Ile, Met, Thr, Pro, Arg, Gly, Ala;

Xaa at position 61 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, orLeu;

Xaa at position 62 is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp;

Xaa at position 63 is Ile, Ser, Arg, Thr, or Leu;

Xaa at position 64 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg;

Xaa at position 65 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp;

Xaa at position 66 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg;

Xaa at position 67 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;

Xaa at position 68 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr,Ser, Ala, Tyr, Phe, Ile, Met or Val;

Xaa at position 69 is Pro, Ala, Thr, Trp, Arg, or Met;

Xaa at position 70 is Cys, Glu, Gly, Arg, Met, or Val;

Xaa at position 71 is Leu, Asn, Val, or Gln;

Xaa at position 72 is Pro, Cys, Arg, Ala, or Lys;

Xaa at position 73 is Leu, Ser, Trp, or Gly;

Xaa at position 74 is Ala, Lys, Arg, Val, or Trp;

Xaa at position 75 is Thr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser;

Xaa at position 76 is Ala, Pro, Ser, Thr, Gly, Asp, Ile, or Met;

Xaa at position 77 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, or His;

Xaa at position 78 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ile orLeu;

Xaa at position 79 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;

Xaa at position 80 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Alaor Pro;

Xaa at position 81 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys,Ser, Ala, Trp, Phe, Ile or Tyr;

Xaa at position 82 is Pro, Lys, Tyr, Gly, Ile, or Thr;

Xaa at position 83 is Ile, Val, Lys, Ala, or Asn;

Xaa at position 84 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser,Phe, Met, Val, Lys, Arg, Tyr or Pro;

Xaa at position 85 is Ile, Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe,or His;

Xaa at position 86 is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, Pro;

Xaa at position 87 is Asp, Pro, Met, Lys, His, Thr, Val, Tyr, Glu, Asn,Ser, Ala, Gly, Ile, Leu or Gln;

Xaa at position 88 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro;

Xaa at position 89 is Asp, or Ser;

Xaa at position 90 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys,Ala, Phe, or Gly;

Xaa at position 91 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys,Ile, Asp, or His;

Xaa at position 92 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro;

Xaa at position 94 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala,or Pro;

Xaa at position 95 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly;

Xaa at position 96 is Lys, Asn, Thr, Leu, Gln, Arg, His, Glu, Ser, Alaor Trp;

Xaa at position 97 is Leu, Ile, Arg, Asp, or Met;

Xaa at position 98 is Thr, Val, Gln, Tyr, Glu, His, Ser, or Phe;

Xaa at position 99 is Phe, Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu,Ile, Val or Asn;

Xaa at position 100 is Tyr, Cys, His, Ser, Trp, Arg, or Leu;

Xaa at position 101 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, orMet;

Xaa at position 102 is Lys, Leu, Pro, Thr, Met, Asp, Val, Glu, Arg, Trp,Ser, Asn, His, Ala, Tyr, Phe, Gln, or Ile;

Xaa at position 103 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro;

Xaa at position 104 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr;

Xaa at position 105 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg;

Xaa at position 106 is Asn, Ala, Pro, Leu, His, Val, or Gln;

Xaa at position 107 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;

Xaa at position 108 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr,or Cys;

Xaa at position 109 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;

and which can additionally have Met- or Met-Ala- preceding the aminoacid in position 1; and wherein from one to three of the amino acidsdesignated by Xaa are different from the corresponding native aminoacids of (1-133) human interleukin-3; or a polypeptide havingsubstantially the same structure and substantially the same biologicalactivity.

Included in the present invention are (15-125)hIL-3 mutant polypeptidesof the Formula VI:

    Asn Cys Xaa Xaa Xaa Xaa Xaa Glu Xaa Xaa Xaa Xaa Leu Xaa Xaa                                                       [SEQ ID NO:20]                               1               5                   10                  15                    - Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Leu Xaa Xaa Glu Xaa                                 20                  25                  30                    - Xaa Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Leu Xaa                                 35                  40                  45                    - Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa                                 50                  55                  60                    - Xaa Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Cys Xaa Pro Xaa Xaa Xaa                                 65                  70                  75                    - Xaa Xaa Xaa Xaa Arg Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asp Xaa                                 80                  85                  90                    - Xaa Xaa Phe Xaa Xaa Lys Leu Xaa Phe Xaa Xaa Xaa Xaa Leu Xaa                                 95                 100                 105                    - Xaa Xaa Xaa Xaa Gln Gln                                                                    110                                                     

wherein

Xaa at position 3 is Ser, Gly, Asp, Met, or Gln;

Xaa at position 4 is Asn, His, Leu, Ile, Phe, Arg, or Gln;

Xaa at position 5 is Met, Phe, Ile, Arg, or Ala;

Xaa at position 6 is Ile or Pro;

Xaa at position 7 is Asp, or Glu;

Xaa at position 9 is Ile, Val, Ala, Leu, or Gly;

Xaa at position 10 is Ile, Val, Phe, or Leu;

Xaa at position 11 is Thr, His, Gly, Gln, Arg, Pro, or Ala;

Xaa at position 12 is His, Phe, Gly, Arg, or Ala;

Xaa at position 14 is Lys, Leu, Gln, Gly, Pro, or Val;

Xaa at position 15 is Gln, Asn, Leu, Arg, or Val;

Xaa at position 16 is Pro, His, Thr, Gly, or Gln;

Xaa at position 17 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln;

Xaa at position 18 is Leu, Arg, Gln, Asn, Gly, Ala, or Glu;

Xaa at position 19 is Pro, Leu, Gln, Ala, or Glu;

Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Ala, Arg, Gln, Glu, Ile,Phe, Thr or Met;

Xaa at position 21 is Leu, Ala, Asn, Pro, Gln, or Val;

Xaa at position 22 is Asp or Leu;

Xaa at position 23 is Phe, Ser, Pro, Trp, or Ile;

Xaa at position 24 is Asn or Ala;

Xaa at position 27 is Asn, Cys, Arg, His, Met, or Pro;

Xaa at position 28 is Gly, Asp, Ser, Cys, Ala, Asn, Ile, Leu, Met, Tyr,or Arg;

Xaa at position 30 is Asp, or Glu;

Xaa at position 31 is Gln, Val, Met, Leu, Thr, Lys, Ala, Asn Glu, Ser orTrp;

Xaa at position 32 is Asp, Phe, Ser, Thr, Cys, Ala, Asn, Gln, Glu, His,Ile, Lys, Tyr, Val or Gly;

Xaa at position 33 is Ile, Val, or His;

Xaa at position 35 is Met, Asn, or Asp;

Xaa at position 36 is Glu, Thr, Ala, Asn, Ser or Asp;

Xaa at position 37 is Asn, Arg, Met, Pro, Ser, Thr, or His;

Xaa at position 38 is Asn or Gly;

Xaa at position 39 is Leu, Met, or Phe;

Xaa at position 40 is Arg, Ala or Ser;

Xaa at position 41 is Arg, Thr, Val, Leu, or Gly;

Xaa at position 42 is Pro, Gly, Cys, Ser, Gln, Ala, Arg, Asn, Glu, His,Leu, Thr, Val or Lys;

Xaa at position 45 is Glu, Tyr, His, Leu, or Arg;

Xaa at position 46 is Ala, Ser, Asn, or Thr;

Xaa at position 47 is Phe or Ser;

Xaa at position 48 is Asn, Val, Pro, Thr, or Ile;

Xaa at position 49 is Arg, Tyr, Lys, Ser, His, or Val;

Xaa at position 50 is Ala or Asn;

Xaa at position 51 is Val, Thr, Leu, or Ser;

Xaa at position 52 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;

Xaa at position 53 is Ser, Phe, Val, Gly, Asn, Ile, or His;

Xaa at position 54 is Leu, Val, Ile, Phe, or His;

Xaa at position 55 is Gln, Ala, Pro, Thr, Glu, Arg, or Gly;

Xaa at position 56 is Asn or Pro;

Xaa at position 57 is Ala, Met, Pro, Arg, Glu, Thr, or Gln;

Xaa at position 58 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;

Xaa at position 59 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, Arg, or Pro;

Xaa at position 60 is Ile or Met;

Xaa at position 61 is Glu, Gly, Asp, Ser, or Gln;

Xaa at position 62 is Ser, Val, Ala, Asn, Glu, Pro, Gly, or Asp;

Xaa at position 63 is Ile, Ser, or Leu;

Xaa at position 65 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp;

Xaa at position 66 is Asn, Val, Gly, Thr, Leu, Glu, or Arg;

Xaa at position 67 is Leu, or Val;

Xaa at position 68 is Leu, Gln, Trp, Arg, Asp, Ala, Asn, Glu, His, Met,Phe, Ser, Thr, Tyr or Val;

Xaa at position 69 is Pro, Ala, Thr, Trp, or Met;

Xaa at position 71 is Leu or Val;

Xaa at position 73 is Leu or Ser;

Xaa at position 74 is Ala, Arg, or Trp;

Xaa at position 75 is Thr, Asp, Glu, His, Asn, or Ser;

Xaa at position 76 is Ala, Asp, or Met;

Xaa at position 77 is Ala, Pro, Ser, Thr, Phe, Leu, or Asp;

Xaa at position 78 is Pro or Ser;

Xaa at position 79 is Thr, Asp, Ser, Pro, Ala, Leu, or Arg;

Xaa at position 81 is His, Pro, Arg, Val, Leu, Gly, Asn, Ile, Phe, Seror Thr;

Xaa at position 82 is Pro or Tyr;

Xaa at position 83 is Ile, Val, or Ala;

Xaa at position 84 is His, Ile, Asn, Leu, Asp, Ala, Thr, Arg, Gln, Glu,Lys, Met, Ser, Tyr, Val or Pro;

Xaa at position 85 is Ile, Leu, Val, or Phe;

Xaa at position 86 is Lys, Leu, His, Arg, Ile, Gln, Pro or Ser;

Xaa at position 87 is Asp, Pro, Met, Lys, His, Thr, Val, Asn, Ile, Leuor Tyr;

Xaa at position 88 is Gly, Glu, Lys, or Ser;

Xaa at position 90 is Trp, Val, Tyr, Met, or Leu;

Xaa at position 91 is Asn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys,Ile, Asp, or His;

Xaa at position 92 is Glu, Ser, Ala, or Gly;

Xaa at position 94 is Arg, Ala, Gln, Ser or Lys;

Xaa at position 95 is Arg, Thr, Glu, Leu, Ser, or Gly;

Xaa at position 98 is Thr, Val, Gln, Glu, His, or Ser;

Xaa at position 100 is Tyr or Trp;

Xaa at position 101 is Leu or Ala;

Xaa at position 102 is Lys, Thr, Met, Val, Trp, Ser, Leu, Ala, Asn, Gln,His, Met, Phe, Tyr or Ile;

Xaa at position 103 is Thr, Ser, or Asn;

Xaa at position 105 is Glu, Ser, Pro, Leu, Thr, or Tyr;

Xaa at position 106 is Asn, Pro, Leu, His, Val, or Gln;

Xaa at position 107 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly;

Xaa at position 108 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr,or Cys;

Xaa at position 109 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;

and which can additionally have Met- or Met-Ala- preceding the aminoacid in position 1; and wherein from one to three of the amino acidsdesignated by Xaa are different from the corresponding amino acids ofnative (1-133) human interleukin-3; or a polypeptide havingsubstantially the same structure and substantially the same biologicalactivity.

Included in the present invention are (15-125)hIL-3 mutant polypeptidesof the Formula VII:

    Asn Cys Xaa Xaa Xaa Ile Xaa Glu Xaa Xaa Xaa Xaa Leu Lys Xaa                                                       [SEQ ID NO:21]                               1               5                   10                  15                    - Xaa Xaa Xaa Xaa Xaa Xaa Asp Xaa Xaa Asn Leu Asn Xaa Glu Xaa                                 20                  25                  30                    - Xaa Xaa Ile Leu Met Xaa Xaa Asn Leu Xaa Xaa Xaa Asn Leu Glu                                 35                  40                  45                    - Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Ile                                 50                  55                  60                    - Glu Xaa Xaa Leu Xaa Xaa Leu Xaa Xaa Cys Xaa Pro Xaa Xaa Thr                                 65                  70                  75                    - Ala Xaa Pro Xaa Arg Xaa Xaa Xaa Xaa Xaa Xaa Xaa Gly Asp Xaa                                 80                  85                  90                    - Xaa Xaa Phe Xaa Xaa Lys Leu Xaa Phe Xaa Xaa Xaa Xaa Leu Glu                                 95                 100                 105                    - Xaa Xaa Xaa Xaa Gln Gln                                                                    110                                                     

wherein

Xaa at position 3 is Ser, Gly, Asp, Met, or Gln;

Xaa at position 4 is Asn, His, or Ile;

Xaa at position 5 is Met or Ile;

Xaa at position 7 is Asp or Glu;

Xaa at position 9 is Ile, Ala, Leu, or Gly;

Xaa at position 10 is Ile, Val, or Leu;

Xaa at position 11 is Thr, His, Gln, or Ala;

Xaa at position 12 is His or Ala;

Xaa at position 15 is Gln, Asn, or Val;

Xaa at position 16 is Pro, Gly, or Gln;

Xaa at position 17 is Pro, Asp, Gly, or Gln;

Xaa at position 18 is Leu, Arg, Gln, Asn, Gly, Ala, or Glu;

Xaa at position 19 is Pro or Glu;

Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Ala, Arg, Gln, Glu, Ile,Phe, Thr or Met;

Xaa at position 21 is Leu, Ala, Asn, Pro, Gln, or Val;

Xaa at position 23 is Phe, Ser, Pro, or Trp;

Xaa at position 24 is Asn or Ala;

Xaa at position 28 is Gly, Asp, Ser, Cys, Ala, Asn, Ile, Leu, Met Tyr orArg;

Xaa at position 30 is Asp or Glu;

Xaa at position 31 is Gln, Val, Met, Leu, Thr, Ala, Asn, Glu, Ser orLys;

Xaa at position 32 is Asp, Phe, Ser, Thr, Ala, Asn, Gln, Glu, His, Ile,Lys, Tyr, Val or Cys;

Xaa at position 36 is Glu, Ala, Asn, Ser or Asp;

Xaa at position 37 is Asn, Arg, Met, Pro, Ser, Thr, or His;

Xaa at position 40 is Arg or Ala;

Xaa at position 41 is Arg, Thr, Val, Leu, or Gly;

Xaa at position 42 is Pro, Gly, Ser, Gln, Ala, Arg, Asn, Glu, Leu, Thr,Val or Lys;

Xaa at position 46 is Ala or Ser;

Xaa at position 48 is Asn, Pro, Thr, or Ile;

Xaa at position 49 is Arg or Lys;

Xaa at position 50 is Ala or Asn;

Xaa at position 51 is Val or Thr;

Xaa at position 52 is Lys or Arg;

Xaa at position 53 is Ser, Phe, or His;

Xaa at position 54 is Leu, Ile, Phe, or His;

Xaa at position 55 is Gln, Ala, Pro, Thr, Glu, Arg, or Gly;

Xaa at position 57 is Ala, Pro, or Arg;

Xaa at position 58 is Ser, Glu, Arg, or Asp;

Xaa at position 59 is Ala or Leu;

Xaa at position 62 is Ser, Val, Ala, Asn, Glu, Pro, or Gly;

Xaa at position 63 is Ile or Leu;

Xaa at position 65 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp;

Xaa at position 66 is Asn, Gly, Glu, or Arg;

Xaa at position 68 is Leu, Gln, Trp, Arg, Asp, Ala, Asn, Glu, His, Ile,Met, Phe, Ser, Thr, Tyr or Val;

Xaa at position 69 is Pro or Thr;

Xaa at position 71 is Leu or Val;

Xaa at position 73 is Leu or Ser;

Xaa at position 74 is Ala or Trp;

Xaa at position 77 is Ala or Pro;

Xaa at position 79 is Thr, Asp, Ser, Pro, Ala, Leu, or Arg;

Xaa at position 81 is His, Pro, Arg, Val, Leu, Gly, Asn, Phe, Ser orThr;

Xaa at position 82 is Pro or Tyr;

Xaa at position 83 is Ile or Val;

Xaa at position 84 is His, Ile, Asn, Leu, Ala, Thr, Arg, Gln, Lys, Met,Ser, Tyr, Val or Pro;

Xaa at position 85 is Ile, Leu, or Val;

Xaa at position 86 is Lys, Arg, Ile, Gln, Pro, or Ser;

Xaa at position 87 is Asp, Pro, Met, Lys, His, Thr, Asn, Ile, Leu orTyr;

Xaa at position 90 is Trp or Leu;

Xaa at position 91 is Asn, Pro, Ala, Ser, Trp, Gln, Tyr, Leu, Lys, Ile,Asp, or His;

Xaa at position 92 is Glu, or Gly;

Xaa at position 94 is Arg, Ala, or Ser;

Xaa at position 95 is Arg, Thr, Glu, Leu, or Ser;

Xaa at position 98 is Thr, Val, or Gln;

Xaa at position 100 is Tyr or Trp;

Xaa at position 101 is Leu or Ala;

Xaa at position 102 is Lys, Thr, Val, Trp, Ser, Ala, His, Met, Phe, Tyror Ile;

Xaa at position 103 is Thr or Ser;

Xaa at position 106 is Asn, Pro, Leu, His, Val, or Gln;

Xaa at position 107 is Ala, Ser, Ile, Asn, Pro, Asp, or Gly;

Xaa at position 108 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr,or Cys;

Xaa at position 109 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;

which can additionally have Met- or Met-Ala- preceding the amino acid inposition 1; and wherein from one to three of the amino acids designatedby Xaa are different from the corresponding amino acids of native(15-125) human interleukin-3; or a polypeptide having substantially thesame structure and substantially the same biological activity.

Included in the present invention are (15-125)hIL-3 mutant polypeptidesof the Formula VIII:

    Asn Cys Xaa Xaa Met Ile Asp Glu Xaa Ile Xaa Xaa Leu Lys Xaa                                                       [SEQ ID NO:22]                               1               5                   10                  15                    - Xaa Pro Xaa Pro Xaa Xaa Asp Phe Xaa Asn Leu Asn Xaa Glu Asp                                 20                  25                  30                    - Xaa Xaa Ile Leu Met Xaa Xaa Asn Leu Arg Xaa Xaa Asn Leu Glu                                 35                  40                  45                    - Ala Phe Xaa Arg Xaa Xaa Lys Xaa Xaa Xaa Asn Ala Ser Ala Ile                                 50                  55                  60                    - Glu Xaa Xaa Leu Xaa Xaa Leu Xaa Pro Cys Leu Pro Xaa Xaa Thr                                 65                  70                  75                    - Ala Xaa Pro Xaa Arg Xaa Pro Ile Xaa Xaa Xaa Xaa Gly Asp Trp                                 80                  85                  90                    - Xaa Glu Phe Xaa Xaa Lys Leu Xaa Phe Tyr Leu Xaa Xaa Leu Glu                                 95                 100                 105                    - Xaa Xaa Xaa Xaa Gln Gln                                                                    110                                                     

wherein

Xaa at position 3 is Ser, Gly, Asp, or Gln;

Xaa at position 4 is Asn, His, or Ile;

Xaa at position 9 is Ile, Ala, Leu, or Gly;

Xaa at position 11 is Thr, His, or Gln;

Xaa at position 12 is His or Ala;

Xaa at position 15 is Gln or Asn;

Xaa at position 16 is Pro or Gly;

Xaa at position 18 is Leu, Arg, Asn, or Ala;

Xaa at position 20 is Leu, Val, Ser, Ala, Arg, Gln, Glu, Ile, Phe, Thror Met;

Xaa at position 21 is Leu, Ala, Asn, or Pro;

Xaa at position 24 is Asn or Ala;

Xaa at position 28 is Gly, Asp, Ser, Ala, Asn, Ile, Leu, Met, Tyr orArg;

Xaa at position 31 is Gln, Val, Met, Leu, Ala, Asn, Glu or Lys;

Xaa at position 32 is Asp, Phe, Ser, Ala, Gln, Glu, His, Val or Thr;

Xaa at position 36 is Glu, Asn, Ser or Asp;

Xaa at position 37 is Asn, Arg, Pro, Thr, or His;

Xaa at position 41 is Arg, Leu, or Gly;

Xaa at position 42 is Pro, Gly, Ser, Ala, Asn, Val, Leu or Gln;

Xaa at position 48 is Asn, Pro, or Thr;

Xaa at position 50 is Ala or Asn;

Xaa at position 51 is Val or Thr;

Xaa at position 53 is Ser or Phe;

Xaa at position 54 is Leu or Phe;

Xaa at position 55 is Gln, Ala, Glu, or Arg;

Xaa at position 62 is Ser, Val, Asn, Pro, or Gly;

Xaa at position 63 is Ile or Leu;

Xaa at position 65 is Lys, Asn, Met, Arg, Ile, or Gly;

Xaa at position 66 is Asn, Gly, Glu, or Arg;

Xaa at position 68 is Leu, Gln, Trp, Arg, Asp, Asn, Glu, His, Met, Phe,Ser, Thr, Tyr or Val;

Xaa at position 73 is Leu or Ser;

Xaa at position 74 is Ala or Trp;

Xaa at position 77 is Ala or Pro;

Xaa at position 79 is Thr, Asp, or Ala;

Xaa at position 81 is His, Pro, Arg, Val, Gly, Asn, Ser or Thr;

Xaa at position 84 is His, Ile, Asn, Ala, Thr, Arg, Gln, Glu, Lys, Met,Ser, Tyr, Val or Leu;

Xaa at position 85 is Ile or Leu;

Xaa at position 86 is Lys or Arg;

Xaa at position 87 is Asp, Pro, Met, Lys, His, Pro, Asn, Ile, Leu orTyr;

Xaa at position 91 is Asn, Pro, Ser, Ile or Asp;

Xaa at position 94 is Arg, Ala, or Ser;

Xaa at position 95 is Arg, Thr, Glu, Leu, or Ser;

Xaa at position 98 is Thr or Gln;

Xaa at position 102 is Lys, Val, Trp, or Ile;

Xaa at position 103 is Thr, Ala, His, Phe, Tyr or Ser;

Xaa at position 106 is Asn, Pro, Leu, His, Val, or Gln;

Xaa at position 107 is Ala, Ser, Ile, Pro, or Asp;

Xaa at position 108 is Gln, Met, Trp, Phe, Pro, His, Ile, or Tyr;

Xaa at position 109 is Ala, Met, Glu, Ser, or Leu;

and which can additionally have Met- or Met-Ala- preceding the aminoacid in position 1; and wherein from one to three of the amino acidsdesignated by Xaa are different from the corresponding amino acids ofnative (1-133)human interleukin-3; or a polypeptide having substantiallythe same structure and substantially the same biological activity.

In Formulas V, VI, VII and VIII the Asn in position 1 corresponds to theAsn in position 15 of native hIL-3 and positions 1 to 111 correspond topositions 15 to 125 in the native hIL-3 sequence shown in FIG. 1.

Also included in the present invention are polypeptides of the followingformula (IX):

                         [SEQ ID NO:129]                                             -                                                                                  1               5                  10                                   (Met).sub.m -Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr                       -             15                  20                                         Ser Trp Val Asn Cys Ser Xaa Met Ile Asp Glu Ile Ile                            - 25                  30                   35                                Xaa His Leu Lys Xaa Pro Pro Xaa Pro Leu Leu Asp Xaa                            -         40                   45                  50                        Asn Asn Leu Asn Xaa Glu Asp Xaa Asp Ile Leu Met Glu                            -                 55                         60                              Xaa Asn Leu Arg Xaa Pro Asn Leu Xaa Xaa Phe Xaa Arg                            -     65                   70                    75                          Ala Val Lys Xaa Leu Xaa Asn Ala Ser Xaa Ile Glu Xaa                            -             80                   85                                        Ile Leu Xaa Asn Leu Xaa Pro Cys Leu Pro Xaa Ala Thr                            - 90                   95                 100                                Ala Ala Pro Xaa Arg His Pro Ile Xaa Ile Lys Xaa Gly                            -         105                 110                 115                        Asp Trp Xaa Glu Phe Arg Xaa Lys Leu Thr Phe Tyr Leu                            -                 120                 125                                    Xaa Thr Leu Glu Xaa Ala Gln Xaa Gln Gln Thr Thr Leu                            -     130                                                                    Ser Leu Ala Ile Phe                                                     

wherein m is 0 or 1; Xaa at position 18 is Asn or Ile; Xaa at position25 is Thr or His; Xaa at position 29 is Gln, Arg, or Val; Xaa atposition 32 is Leu, Ala, or Asn; Xaa at position 37 is Phe, Pro, or Ser;Xaa at position 42 is Glu, Ala, or Ser; Xaa at position 45 is Gln, Val,or Met; Xaa at position 51 is Asn or Arg; Xaa at position 55 is Arg,Leu, or Thr; Xaa at position 59 is Glu or Leu; Xaa at position 60 is Alaor Ser; Xaa at position 62 is Asn or Val; Xaa at position 67 is Ser,Asn, or His; Xaa at position 69 is Gln or Glu; Xaa at position 73 is Alaor Gly; Xaa at position 76 is Ser or Ala; Xaa at position 79 is Lys orArg; Xaa at position 82 is Leu, Glu, or Val; Xaa at position 87 is Leuor Ser; Xaa at position 93 is Pro or Ser; Xaa at position 98 is His,Ile, or Thr; Xaa at position 101 is Asp or Ala; Xaa at position 105 isAsn or Glu; Xaa at position 109 is Arg or Glu; Xaa at position 116 isLys or Val; Xaa at position 120 is Asn, Gln, or His; Xaa at position 123is Ala or Glu; wherein from one to three of the amino acids designatedby Xaa are different from the corresponding amino acids of native humaninterleukin-3; or a polypeptide having substantially the same structureand substantially the same biological activity.

Polypeptides of the present invention include those (15-125)hIL-3muteins of the following formula (X):

                         [SEQ ID NO:130]                                             -                                                                                        1               5                                                 (Met.sub.m -Ala.sub.n).sub.p -Asn Cys Ser Xaa Met Ile Asp Glu Ile             -  10                 15                   20                                Ile Xaa His Leu Lys Xaa Pro Pro Xaa Pro Leu Leu Asp                            -         25                   30                   35                       Xaa Asn Asn Leu Asn Xaa Glu Asp Xaa Asp Ile Leu Met                            -                 40                   45                                    Glu Xaa Asn Leu Arg Xaa Pro Asn Leu Xaa Xaa Phe Xaa                            -      50                 55                   60                            Arg Ala Val Lys Xaa Leu Xaa Asn Ala Ser Xaa Ile Glu                            -             65                   70                                        Xaa Ile Leu Xaa Asn Leu Xaa Pro Cys Leu Pro Xaa Ala                            -  75                 80                   85                                Thr Ala Ala Pro Xaa Arg His Pro Ile Xaa Ile Lys Xaa                            -          90                  95                  100                       Gly Asp Trp Xaa Glu Phe Arg Xaa Lys Leu Thr Phe Tyr                            -                 105                  110                                   Leu Xaa Thr Leu Glu Xaa Ala Gln Xaa Gln Gln                              

wherein m is 0 or 1; n is 0 or 1; p is 0 or 1; Xaa at position 4 is Asnor Ile; Xaa at position 11 is Thr or His; Xaa at position 15 is Gln,Arg, or Val; Xaa at position 18 is Leu, Ala, or Asn; Xaa at position 23is Phe, Pro, or Ser; Xaa at position 28 is Glu, Ala, or Ser; Xaa atposition 31 is Gln, Val, or Met; Xaa at position 37 is Asn or Arg; Xaaat position 41 is Arg, Leu, or Thr; Xaa at position 45 is Glu or Leu;Xaa at position 46 is Ala or Ser; Xaa at position 48 is Asn or Val; Xaaat position 53 is Ser, Asn, or His; Xaa at position 55 is Gln or Glu;Xaa at position 59 is Ala or Gly; Xaa at position 62 is Ser or Ala; Xaaat position 65 is Lys or Arg; Xaa at position 68 is Leu, Glu, or Val;Xaa at position 73 is Leu or Ser; Xaa at position 79 is Pro or Ser; Xaaat position 84 is His, Ile, or Thr; Xaa at position 87 is Asp or Ala;Xaa at position 91 is Asn or Glu; Xaa at position 95 is Arg or Glu; Xaaat position 102 is Lys or Val; Xaa at position 106 is Asn, Gln, or His;Xaa at position 109 is Ala or Glu;

wherein from one to three of the amino acids designated by Xaa aredifferent from the corresponding amino acids of native (15-125)humaninterleukin-3; or a polypeptide having substantially the same structureand substantially the same biological activity.

The present invention includes polypeptides of Formula IX and Formula Xabove wherein from one to three of the amino acids designated by Xaa aredifferent from the corresponding amino acids of native humaninterleukin-3 or native (15-125) human interleukin-3; or a polypeptidehaving substantially the same structure and substantially the samebiological activity.

"Mutant amino acid sequence," "mutant protein" or "mutant polypeptide"refers to a polypeptide having an amino acid sequence which varies froma native sequence or is encoded by a nucleotide sequence intentionallymade variant from a native sequence. "Mutant protein," "variant protein"or "mutein" means a protein comprising a mutant amino acid sequence andincludes polypeptides which differ from the amino acid sequence ofnative hIL-3 due to amino acid deletions, substitutions, or both."Native sequence" refers to an amino acid or nucleic acid sequence whichis identical to a wild-type or native form of a gene or protein.

Human IL-3 can be characterized by its ability to stimulate colonyformation by human hematopoietic progenitor cells. The colonies formedinclude erythroid, granulocyte, megakaryocyte, granulocytic macrophagesand mixtures thereof. Human IL-3 has demonstrated an ability to restorebone marrow function and peripheral blood cell populations totherapeutically beneficial levels in studies performed initially inprimates and subsequently in humans (Gillio, A. P., et al. (1990);Ganser, A., et al. (1990); Falk, S., et al. (1991). Additionalactivities of hIL-3 include the ability to stimulate leukocyte migrationand chemotaxis; the ability to prime human leukocytes to produce highlevels of inflammatory mediators like leukotrienes and histamine; theability to induce cell surface expression of molecules needed forleukocyte adhesion; and the ability to trigger dermal inflammatoryresponses and fever. Many or all of these biological activities of hIL-3involve signal transduction and high affinity receptor binding. Mutantpolypeptides of the present invention may exhibit useful properties suchas having similar or greater biological activity when compared to nativehIL-3 or by having improved half-life or decreased adverse side effects,or a combination of these properties. They may also be useful asantagonists. hIL-3 mutant polypeptides which have little or no activitywhen compared to native hIL-3 may still be useful as antagonists, asantigens for the production of antibodies for use in immunology orimmunotherapy, as genetic probes or as intermediates used to constructother useful hIL-3 muteins. Since hIL-3 functions by binding to itsreceptor(s) and triggering second messages resulting in competent signaltransduction, hIL-3 muteins of this invention may be useful in helpingto determine which specific amino acid sequences are responsible forthese activities.

The novel hIL-3 mutant polypeptides of the present invention willpreferably have at least one biological property of human IL-3 or of anIL-3-like growth factor and may have more than one IL-3-like biologicalproperty, or an improved property, or a reduction in an undesirablebiological property of human IL-3. Some mutant polypeptides of thepresent invention may also exhibit an improved side effect profile. Forexample, they may exhibit a decrease in leukotriene release or histaminerelease when compared to native hIL-3 or (15-125) hIL-3. Such hIL-3 orhIL-3-like biological properties may include one or more of thefollowing biological characteristics and in vivo and in vitroactivities.

One such property is the support of the growth and differentiation ofprogenitor cells committed to erythroid, lymphoid, and myeloid lineages.For example, in a standard human bone marrow assay, an IL-3-likebiological property is the stimulation of granulocytic type colonies,megakaryocytic type colonies, monocyte/macrophage type colonies, anderythroid bursts. Other IL-3-like properties are the interaction withearly multipotential stem cells, the sustaining of the growth ofpluripotent precursor cells, the ability to stimulate chronicmyelogenous leukemia (CML) cell proliferation, the stimulation ofproliferation of mast cells, the ability to support the growth ofvarious factor-dependent cell lines, and the ability to trigger immaturebone marrow cell progenitors. Other biological properties of IL-3 havebeen disclosed in the art. Human IL-3 also has some biologicalactivities which may in some cases be undesirable, for example theability to stimulate leukotriene release and the ability to stimulateincreased histamine synthesis in spleen and bone marrow cultures and invivo.

Biological activity of hIL-3 and hIL-3 mutant proteins of the presentinvention is determined by DNA synthesis by human acute myelogenousleukemia cells (AML). The factor-dependent cell line AML 193 was adaptedfor use in testing biological activity.

One object of the present invention is to provide hIL-3 muteins andhIL-3 deletion muteins with one or more amino acid substitutions in thepolypeptide sequence which have similar or improved biological activityin relation to native hIL-3 or native (15-125)hIL-3.

The present invention includes mutant polypeptides comprising minimallyamino acid residues 15 to 118 of hIL-3 with or without additional aminoacid extensions to the N-terminus and/or C-terminus which furthercontain from one to three or more amino acid substitutions in the aminoacid sequence of the polypeptide. It has been found that the(15-125)hIL-3 mutant is more soluble than is hIL-3 when expressed in thecytoplasm of E. coli, and the protein is secreted to the periplasm in E.coli at higher levels compared to native hIL-3.

When expressed in the E. coli cytoplasm, the above-mentioned mutanthIL-3 polypeptides of the present invention may also be constructed withMet-Ala- at the N-terminus so that upon expression the Met is cleavedoff leaving Ala at the N-terminus. These mutant hIL-3 polypeptides mayalso be expressed in E. coli by fusing a signal peptide to theN-terminus. This signal peptide is cleaved from the polypeptide as partof the secretion process. Secretion in E. coli can be used to obtain thecorrect amino acid at the N-terminus (e.g., Asn¹⁵ in the (15-125) hIL-3polypeptide) due to the precise nature of the signal peptidase. This isin contrast to the heterogeneity often observed at the N-terminus ofproteins expressed in the cytoplasm in E. coli.

The hIL-3 mutant polypeptides of the present invention may have hIL-3 orhIL-3-like activity. For example, they may possess one or more of thebiological activities of native hIL-3 and may be useful in stimulatingthe production of hematopoietic cells by human or primate progenitorcells. The hIL-3 muteins of the present invention and pharmaceuticalcompositions containing them may be useful in the treatment ofconditions in which hematopoietic cell populations have been reduced ordestroyed due to disease or to treatments such as radiation orchemotherapy.

hIL-3 muteins of the present invention may also be useful as antagonistswhich block the hIL-3 receptor by binding specifically to it andpreventing binding of the agonist.

One potential advantage of the (15-125) hIL-3 muteins of the presentinvention, particularly those which retain activity similar to or betterthan that of native hIL-3, is that it may be possible to use a smalleramount of the biologically active mutein to produce the desiredtherapeutic effect. This may make it possible to reduce the number oftreatments necessary to produce the desired therapeutic effect. The useof smaller amounts may also reduce the possibility of any potentialantigenic effects or other possible undesirable side effects. Forexample, if a desired therapeutic effect can be achieved with a smalleramount of polypeptide it may be possible to reduce or eliminate sideeffects associated with the administration of native IL-3 such as thestimulation of leukotriene and/or histamine release. The hIL-3 muteinsof the present invention may also be useful in the activation of stemcells or progenitors which have low receptor numbers. Pharmaceuticalcompositions containing hIL-3 muteins of the present invention can beadministered parenterally, intravenously, or subcutaneously.

In variants which contain an additional cysteine the presence of thecysteine permits the labeling of the protein with ricin which permitstargeting ricin and other toxins or tracers using a sulfhydryl linkageto the hIL-3 receptor.

As another aspect of the present invention, there is provided a novelmethod for producing the novel family of human IL-3 muteins. The methodof the present invention involves culturing a suitable cell or cellline, which has been transformed with a vector containing a DNA sequencecoding for expression of a novel hIL-3 mutant polypeptide. Suitablecells or cell lines may be bacterial cells. For example, the variousstrains of E. coli are well-known as host cells in the field ofbiotechnology. Examples of such strains include E. coli strains JM101[Yanish-Perron, et al. (1985)] and MON105 [Obukowicz, et al. (1992)].Various strains of B. subtilis may also be employed in this method. Manystrains of yeast cells known to those skilled in the art are alsoavailable as host cells for expression of the polypeptides of thepresent invention.

Also suitable for use in the present invention are mammalian cells, suchas Chinese hamster ovary cells (CHO). General methods for expression offoreign genes in mammalian cells are reviewed in: Kaufman, R. J. (1987)High level production of proteins in mammalian cells, in GeneticEngineering, Principles and Methods, Vol. 9, J. K. Setlow, editor,Plenum Press, New York. An expression vector is constructed in which astrong promoter capable of functioning in mammalian cells drivestranscription of a eukaryotic secretion signal peptide coding region,which is translationally fused to the coding region for the hIL-3variant. For example, plasmids such as pcDNA I/Neo, pRc/RSV, and pRc/CMV(obtained from Invitrogen Corp., San Diego, Calif.) can be used. Theeukaryotic secretion signal peptide coding region can be from the hIL-3gene itself or it can be from another secreted mammalian protein (Bayne,M. L. et al. (1987) Proc. Natl. Acad. Sci. USA 84, 2638-2642). Afterconstruction of the vector containing the hIL-3 variant gene, the vectorDNA is transfected into mammalian cells. Such cells can be, for example,the COS7, HeLa, BHK, CHO, or mouse L lines. The cells can be cultured,for example, in DMEM media (JRH Scientific). The hIL-3 variant secretedinto the media can be recovered by standard biochemical approachesfollowing transient expression 24-72 hours after transfection of thecells or after establishment of stable cell lines following selectionfor neomycin resistance. The selection of suitable mammalian host cellsand methods for transformation, culture, amplification, screening andproduct production and purification are known in the art. See, e.g.,Gething and Sambrook, Nature, 293:620-625 (1981), or alternatively,Kaufman et al, Mol. Cell. Biol., 5(7):1750-1759 (1985) or Howley et al.,U.S. Pat. No. 4,419,446. Another suitable mammalian cell line is themonkey COS-1 cell line. A similarly useful mammalian cell line is theCV-1 cell line.

Where desired, insect cells may be utilized as host cells in the methodof the present invention. See, e.g. Miller et al, Genetic Engineering,8:277-298 (Plenum Press 1986) and references cited therein. In addition,general methods for expression of foreign genes in insect cells usingBaculovirus vectors are described in: Summers, M. D. and Smith, G. E.(1987)--A manual of methods for Baculovirus vectors and insect cellculture procedures, Texas Agricultural Experiment Station Bulletin No.1555. An expression vector is constructed comprising a Baculovirustransfer vector, in which a strong Baculovirus promoter (such as thepolyhedron promoter) drives transcription of a eukaryotic secretionsignal peptide coding region, which is translationally fused to thecoding region for the hIL-3 variant polypeptide. For example, theplasmid pVL1392 (obtained from Invitrogen Corp., San Diego, Calif.) canbe used. After construction of the vector carrying the hIL-3 variantgene, two micrograms of this DNA is cotransfected with one microgram ofBaculovirus DNA (see Summers & Smith, 1987) into insect cells, strainSF9. Pure recombinant Baculovirus carrying the hIL-3 variant is used toinfect cells cultured, for example, in Excell 401 serum-free medium (JRHBiosciences, Lenexa, Kans.). The hIL-3 variant secreted into the mediumcan be recovered by standard biochemical approaches.

Another aspect of the present invention provides plasmid DNA vectors foruse in the method of expression of these novel hIL-3 muteins. Thesevectors contain the novel DNA sequences described above which code forthe novel polypeptides of the invention. Appropriate vectors which cantransform microorganisms capable of expressing the hIL-3 muteins includeexpression vectors comprising nucleotide sequences coding for the hIL-3muteins joined to transcriptional and translational regulatory sequenceswhich are selected according to the host cells used.

Vectors incorporating modified sequences as described above are includedin the present invention and are useful in the production of the hIL-3mutant polypeptides. The vector employed in the method also containsselected regulatory sequences in operative association with the DNAcoding sequences of the invention and capable of directing thereplication and expression thereof in selected host cells.

The present invention also includes the construction and expression of(15-125)human interleukin-3 muteins having one or more amino acidsubstitutions in secretion vectors that optimize accumulation ofcorrectly folded, active polypeptide. While many heterologous proteinshave been secreted in E. coli there is still a great deal ofunpredictability and limited success (Stader and Silhavy 1990).Full-length hIL-3 is such a protein, where attempts to secrete theprotein in E. coli resulted in low levels of secretion. Secretion of thevariant (15-125) hIL-3 mutant polypeptides of the present invention as afusion with a signal peptide such as lamB results in correctly foldedprotein that can be removed from the periplasm of E. coli by osmoticshock fractionation. This property of the variant (15-125) hIL-3 muteinsallows for the direct and rapid screening for bioactivity of thesecreted material in the crude osmotic shock fraction, which is asignificant advantage. Furthermore, it provides a means of using the(15-125)hIL-3 muteins to conduct structure activity relationship (SAR)studies of the hIL-3 molecule. A further advantage of secretion of(15-125) hIL-3 muteins fused to the lamB signal peptide is that thesecreted polypeptide has the correct N-terminal amino acid (Asn) due tothe precise nature of the cleavage of the signal peptide by signalpeptidase, as part of the secretion process.

The (15-125)hIL-3 muteins of the present invention may include hIL-3polypeptides having Met-, Ala- or Met-Ala- attached to the N-terminus.When the muteins are expressed in E. coli, polypeptides with and withoutMet attached to the N-terminus are obtained. The methionine can in somecases be removed by methionine aminopeptidase.

Amino terminal sequences of some of the hIL-3 muteins made in E. coliwere determined using the method described by Hunkapillar et al.,(1983). It was found that hIL-3 proteins made in E. coli from genesencoding Met-(15-125)hIL-3 were isolated as Met-(15-125) hIL-3. Proteinsproduced from genes encoding Met-Ala-(15-125) hIL-3 were produced asAla-(15-125) hIL-3. The N-termini of proteins made in the cytoplasm ofE. coli are affected by posttranslational processing by methionineaminopeptidase (Ben-Bassat et al., 1987) and possibly by otherpeptidases.

One method of creating the preferred hIL-3 (15-125) mutant genes iscassette mutagenesis [Wells, et al. (1985)] in which a portion of thecoding sequence of hIL-3 in a plasmid is replaced with syntheticoligonucleotides that encode the desired amino acid substitutions in aportion of the gene between two restriction sites. In a similar manneramino acid substitutions could be made in the full-length hIL-3 gene, orgenes encoding variants of hIL-3 in which from 1 to 14 amino acids havebeen deleted from the N-terminus and/or from 1 to 15 amino acids havebeen deleted from the C-terminus. When properly assembled theseoligonucleotides would encode hIL-3 variants with the desired amino acidsubstitutions and/or deletions from the N-terminus and/or C-terminus.These and other mutations could be created by those skilled in the artby other mutagenesis methods including; oligonucleotide-directedmutagenesis [Zoller and Smith (1982, 1983, 1984), Smith (1985), Kunkel(1985), Taylor, et al. (1985), Deng and Nickoloff (1992)] or polymerasechain reaction (PCR) techniques [Saiki, (1985)].

Pairs of complementary synthetic oligonucleotides encoding portions ofthe amino terminus of the hIL-3 gene can be made and annealed to eachother. Such pairs would have protruding ends compatible with ligation toNcoI at one end. The NcoI site would include the codon for the initiatormethionine. At the other end of oligonucleotide pairs, the protruding(or blunt) ends would be compatible with a restriction site that occurswithin the coding sequence of the hIL-3 gene. The DNA sequence of theoligonucleotide would encode sequence for amino acids of hIL-3 with theexception of those substituted and/or deleted from the sequence.

The NcoI enzyme and the other restriction enzymes chosen should haverecognition sites that occur only once in the DNA of the plasmid chosen.Plasmid DNA can be treated with the chosen restriction endonucleasesthen ligated to the annealed oligonucleotides. The ligated mixtures canbe used to transform competent JM101 cells to resistance to anappropriate antibiotic. Single colonies can be picked and the plasmidDNA examined by restriction analysis and/or DNA sequencing to identifyplasmids with mutant hIL-3 genes.

One example of a restriction enzyme which cleaves within the codingsequence of the hIL-3 gene is ClaI whose recognition site is at codons20 and 21. The use of ClaI to cleave the sequence of hIL-3 requires thatthe plasmid DNA be isolated from an E. coli strain that fails tomethylate adenines in the DNA at GATC recognition sites. This is becausethe recognition site for ClaI, ATCGAT, occurs within the sequenceGATCGAT which occurs at codons 19, 20 and 21 in the hIL-3 gene. The A inthe GATC sequence is methylated in most E. coli host cells. Thismethylation prevents ClaI from cleaving at that particular sequence. Anexample of a strain that does not methylate adenines is GM48.

Interpretation of activity of single amino acid mutants in IL-3 (15-125)

As illustrated in Tables 6 and 9, there are certain positions in theIL-3 (15-125) molecule which are intolerant of substitutions, in thatmost or all substitutions at these positions resulted in a considerabledecrease in bioactivity. There are two likely classes of such"down-mutations": mutations that affect overall protein structure, andmutations that interfere directly with the interaction between the IL-3molecule and its receptor. Mutations affecting the three-dimensionalstructure of the protein will generally lie in the interior of theprotein, while mutations affecting receptor binding will generally lieon the surface of the protein. Although the three-dimensional structureof IL-3 is unknown, there are simple algorithms which can aid in theprediction of the structure. One such algorithm is the use of "helicalwheels" (Kaiser, E. T. & Kezdy, F. J., Science, 223:249-255 (1984)). Inthis method, the presence of alpha helical protein structures can bepredicted by virtue of their amphipathic nature. Helices in globularproteins commonly have an exposed hydrophilic side and a buriedhydrophobic side. As a broad generalization, in globular proteins,hydrophobic residues are present in the interior of the protein, andhydrophilic residues are present on the surface. By displaying the aminoacid sequence of a protein on such a "helical wheel" it is possible toderive a model for which amino acids in alpha helices are exposed andwhich are buried in the core of the protein. Such an analysis of theIL-3 (15-125) molecule predicts that the following helical residues areburied in the core:

    ______________________________________                                          M19, I20, I23, I24, L27, L58, F61, A64, L68, A71,                            I74, I77, L78, L81, W104, F107, L111, Y114, L115, L118.                      ______________________________________                                    

In addition, cysteine residues at positions 16 and 84 are linked by adisulfide bond, which is important for the overall structure or"folding" of the protein. Finally, mutations which result in a majordisruption of the protein structure may be expressed at low level in thesecretion system used in our study, for a variety of reasons: eitherbecause the mis-folded protein is poorly recognized by the secretionmachinery of the cell; because mis-folding of the protein results inaggregation, and hence the protein cannot be readily extracted from thecells; or because the mis-folded protein is more susceptible todegradation by cellular proteases. Hence, a block in secretion mayindicate which positions in the IL-3 molecule which are important formaintenance of correct protein structure.

In order to retain the activity of a variant of IL-3, it is necessary toretain both the structural integrity of the protein, and retain thespecific residues important for receptor contact. Hence it is possibleto define specific amino acid residues in IL-3 (15-125) which must beretained in order to preserve biological activity.

Residues predicted to be important for interaction with the receptor:D21, E22, E43, D44, L48, R54, R94, D103, K110, F113.

Residues predicted to be structurally important: C16, L58, F61, A64,I74, L78, L81, C84, P86, P92, P96, F107, L111, L115, L118.

The hIL-3 muteins of the present invention may be useful in thetreatment of diseases characterized by a decreased levels of eithermyeloid, erythroid, lymphoid, or megakaryocyte cells of thehematopoietic system or combinations thereof. In addition, they may beused to activate mature myeloid and/or lymphoid cells. Among conditionssusceptible to treatment with the polypeptides of the present inventionis leukopenia, a reduction in the number of circulating leukocytes(white cells) in the peripheral blood. Leukopenia may be induced byexposure to certain viruses or to radiation. It is often a side effectof various forms of cancer therapy, e.g., exposure to chemotherapeuticdrugs and of infection or hemorrhage. Therapeutic treatment ofleukopenia with these hIL-3 mutant polypeptides of the present inventionmay avoid undesirable side effects caused by treatment with presentlyavailable drugs.

The hIL-3 muteins of the present invention may be useful in thetreatment of neutropenia and, for example, in the treatment of suchconditions as aplastic anemia, cyclic neutropenia, idiopathicneutropenia, Chdiak-Higashi syndrome, systemic lupus erythematosus(SLE), leukemia, myelodysplastic syndrome and myelofibrosis.

Many drugs may cause bone marrow suppression or hematopoieticdeficiencies. Examples of such drugs are AZT, DDI, alkylating agents andanti-metabolites used in chemotherapy, antibiotics such aschloramphenicol, penicillin and sulfa drugs, phenothiazones,tranquilizers such as meprobamate, and diuretics. The hIL-3 muteins ofthe present invention may be useful in preventing or treating the bonemarrow suppression or hematopoietic deficiencies which often occur inpatients treated with these drugs.

Hematopoietic deficiencies may also occur as a result of viral,microbial or parasitic infections and as a result of treatment for renaldisease or renal failure, e.g., dialysis. The hIL-3 muteins of thepresent invention may be useful in treating such hematopoieticdeficiency.

The treatment of hematopoietic deficiency may include administration ofthe hIL-3 mutein of a pharmaceutical composition containing the hIL-3mutein to a patient. The hIL-3 muteins of the present invention may alsobe useful for the activation and amplification of hematopoieticprecursor cells by treating these cells in vitro with the muteins of thepresent invention prior to injecting the cells into a patient.

Various immunodeficiencies e.g., in T and/or B lymphocytes, or immunedisorders, e.g., rheumatoid arthritis, may also be beneficially affectedby treatment with the hIL-3 mutant polypeptides of the presentinvention. Immunodeficiencies may be the result of viral infections e.g.HTLVI, HTLVII, HTLVIII, severe exposure to radiation, cancer therapy orthe result of other medical treatment. The hIL-3 mutant polypeptides ofthe present invention may also be employed, alone or in combination withother hematopoietins, in the treatment of other blood cell deficiencies,including thrombocytopenia (platelet deficiency), or anemia. Other usesfor these novel polypeptides are in the treatment of patients recoveringfrom bone marrow transplants in vivo and ex vivo, and in the developmentof monoclonal and polyclonal antibodies generated by standard methodsfor diagnostic or therapeutic use.

Other aspects of the present invention are methods and therapeuticcompositions for treating the conditions referred to above. Suchcompositions comprise a therapeutically effective amount of one or moreof the hIL-3 muteins of the present invention in a mixture with apharmaceutically acceptable carrier. This composition can beadministered either parenterally, intravenously or subcutaneously. Whenadministered, the therapeutic composition for use in this invention ispreferably in the form of a pyrogen-free, parenterally acceptableaqueous solution. The preparation of such a parenterally acceptableprotein solution, having due regard to pH, isotonicity, stability andthe like, is within the skill of the art.

The dosage regimen involved in a method for treating the above-describedconditions will be determined by the attending physician consideringvarious factors which modify the action of drugs, e.g. the condition,body weight, sex and diet of the patient, the severity of any infection,time of administration and other clinical factors. Generally, a dailyregimen may be in the range of 0.2-150 μg/kg of non-glycosylated IL-3protein per kilogram of body weight. This dosage regimen is referencedto a standard level of biological activity which recognizes that nativeIL-3 generally possesses an EC₅₀ at or about 10 picoMolar to 100picoMolar in the AML proliferation assay described herein. Therefore,dosages would be adjusted relative to the activity of a given mutein vs.the activity of native (reference) IL-3 and it would not be unreasonableto note that dosage regimens may include doses as low as 0.1 microgramand as high as 1 milligram per kilogram of body weight per day. Inaddition, there may exist specific circumstances where dosages of IL-3mutein would be adjusted higher or lower than the range of 10-200micrograms per kilogram of body weight. These include co-administrationwith other CSF or growth factors; co-administration withchemotherapeutic drugs and/or radiation; the use of glycosylated IL-3mutein; and various patient-related issues mentioned earlier in thissection. As indicated above, the therapeutic method and compositions mayalso include co-administration with other human factors. A non-exclusivelist of other appropriate hematopoietins, CSFs and interleukins forsimultaneous or serial co-administration with the polypeptides of thepresent invention includes GM-CSF, CSF-1, G-CSF, Meg-CSF, M-CSF,erythropoietin (EPO), IL-1, IL-4, IL-2, IL-5, IL-6, IL-7, IL-8, IL-9,IL-10, IL-11, LIF, B-cell growth factor, B-cell differentiation factorand eosinophil differentiation factor, stem cell factor (SCF) also knownas steel factor or c-kit ligand, or combinations thereof. The dosagerecited above would be adjusted to compensate for such additionalcomponents in the therapeutic composition. Progress of the treatedpatient can be monitored by periodic assessment of the hematologicalprofile, e.g., differential cell count and the like.

Materials and methods for hIL-3 Mutein Expression in E. coli

Unless noted otherwise, all specialty chemicals were obtained from SigmaCo., (St. Louis, Mo.). Restriction endonucleases, T4 poly-nucleotideskinase, E. coli DNA polymerase I large fragment (Klenow) and T4 DNAligase were obtained from New England Biolabs (Beverly, Mass.) orBoehringer Mannheim (Indianapolis, Ind.). All chemicals and enzymes wereused according to manufacturer's directions.

Escherichia coli strains

Strain JM101: delta (pro lac), supE, thi, F'(traD36, proAB, lacI-Q,lacZdeltaM15) (Messing, 1979). This strain can be obtained from theAmerican Type Culture Collection (ATCC), 12301 Parklawn Drive,Rockville, Md. 20852, accession number 33876. MON 105 (W3110 rpoH358)(Obukowicz, et al., 1992) is a derivative of W3110 (Bachmann, 1972) andhas been assigned ATCC accession number 55204. Strain GM48: dam-3,dcm-6, gal, ara, lac, thr, leu, tonA, tsx (Marinus, 1973) was used tomake plasmid DNA that is not methylated at the sequence GATC.

Genes and plasmids

The gene used for hIL-3 production in E. coli was obtained from BritishBiotechnology Incorporated, Cambridge, England, catalogue number BBG14.This gene is carried on a pUC based plasmid designated pP0518. The humanIL-3 gene sequence is from Yang, et al. (1986).

The plasmids used for production of hIL-3 in E. coli contain geneticelements whose use has been described (Olins et al., 1988; Olins andRangwala, 1990). The replicon used is that of pBR327 [(Bolivar et al.(1977); Soberon et al., 1980] which is maintained at a copy number ofabout 50 in the cell (Covarrubias, et al., (1981)). A gene encoding thebeta-lactamase protein is present on the plasmids. This protein confersampicillin resistance on the cell. This resistance serves as aselectable phenotype for the presence of the plasmid in the cell.

Intracellular expression plasmids:

For cytoplasmic (intracellular) expression vectors the transcriptionpromoter was derived from the recA gene of E. coli (Sancar et al.,1980). This promoter, designated precA, is contained on 72 base pairs(bp) BglII, BamHI fragment which includes the RNA polymerase bindingsite and the lexA repressor binding site (the operator). This segment ofDNA provides high level transcription that is regulated even when therecA promoter is on a plasmid with the pBR327 origin of replication(Olins et al., 1988) incorporated herein by reference.

Secretion expression plasmids:

In secretion expression plasmids the transcription promoter was derivedfrom the ara B, A, and D genes of E. coli (Greenfield et al., 1978).This promoter is designated pAraBAD and is contained on a 323 base pairSacII, BglII restriction fragment. The lamb secretion leader (Wong etal., 1988, Clement et al., 1981) was fused to the N-terminus of thehIL-3 gene at the recognition sequence for the enzyme NcoI (5'CCATGG3').The hIL-3 genes used were engineered to have a HindIII recognition site(5'AAGCTT3') following the coding sequence of the gene. Downstream ofthe gene is a 550 bp fragment containing the origin of replication ofthe single stranded phage f1 [Olins and Rangwala (1989)].

These hIL-3 variants were expressed as a fusion with the lamB signalpeptide operatively joined to the araBAD promoter (Greenfield, 1978) andthe g10-L ribosome binding site (Olins et al. 1988). The signal peptideis removed as part of the secretion process. The processed form wasselectively released from the periplasm by osmotic shock as a correctlyfolded and fully active molecule. Secretion of (15-125) hIL-3 wasfurther optimized by using low inducer (arabinose) concentration and bygrowth at 30° C. These conditions resulted in lower accumulation levelsof unprocessed lamB signal peptide (15-125) hIL-3 fusion, maximalaccumulation levels of processed (15-125) hIL-3 and selective release of(15-125) hIL-3 by osmotic shock fractionation. The use of a tightlyregulated promoter such as araBAD from which the transcription level andhence the expression level can be modulated allowed for the optimizationof secretion of (15-125) hIL-3.

The ribosome binding site (RBS) used is that from gene 10 of phage T7(Olins et al., 1988). This is encoded in a 100 base pair (bp) fragmentplaced adjacent to precA. In the plasmids used herein, the recognitionsequence for the enzyme NcoI (5'CCATGG3') follows the g10-L RBS. It isat this NcoI site that the hIL-3 genes are joined to the plasmid. It isexpected that the nucleotide sequence at this junction will berecognized in mRNA as a functional start site for translation (Olins etal., 1988). The hIL-3 genes used were engineered to have a HindIIIrecognition site (5'AAGCTT3') following the coding sequence of the gene.Downstream of the gene is a 550 base pair fragment containing the originof replication of the single stranded phage f1 (Dente et al., 1983;Olins, et al., 1990) both incorporated herein by reference. A plasmidcontaining these elements is pMON2341. Another plasmid containing theseelements is pMON5847 which has been deposited at the American TypeCulture Collection, 12301 Parklawn Drive, Rockville, Md. 20852 under theaccession number ATCC 68912.

Synthesis of Oligonucleotides

Oligonucleotides were synthesized by the cyanoethyl method (Adams et al.1983, McBride, et al. 1983, Sinba et al., 1984) on NucleotideSynthesizer model 380A or 380B from Applied Biosystems, Inc. (FosterCity, Calif.). Some oligonucleotides were purchased from GenosysBiotechnologies Inc. (The Woodlands, Tex.) or Midland Certified ReagentCo. (Midland, Tex.). The degenerate oligonucleotides were synthesized bymachine mixing an equal molar ratio of the desired nucleosides in thecondensation reaction at degenerate positions. Oligonucleotides werepurified by polyacrylamide gel electrophoresis at concentrations from12-20% (19:1 crosslinked) in 0.5× Tris borate (TBE) buffer (0.045 MTris, 0.045 M boric acid, 1.25 mM EDTA) as described by Atkinson (1984).The oligonucleotides were desalted by passage through a Nensorb 20column obtained from DuPont/New England Nuclear (Boston, Mass.) using aPREP Automated Sample Processor obtained from DuPont, Co. (Wilmington,Del.).

Quantitation of synthetic oligonucleotides

Synthetic oligonucleotides were resuspended in water (100 μl) andquantitated by reading the absorbance at 260 nm on a Beckman DU40Spectrophotometer (Irvine, Calif.) using a one centimeter by onemillimeter quartz cuvette (Maniatis, 1982). The concentration wasdetermined using an extinction coefficient of 1×10⁴ (Voet et al., 1963;Mahler and Cordes, 1966). The oligonucleotide was then diluted to thedesired concentration.

Quantitation of synthetic DNA fragments can also be achieved by adding10 to 100 picomoles of DNA to a solution containing kinase buffer (25 mMTris pH 8.0, 10 mM MgCl₂, 10 mM DTT and 2 mM spermidine). To thereaction mix is added ATP to 20 micromolar, ATP radiolabeled at thegamma phosphate (5000-10,0000 dpm/pmol) and 5 units of T4 polynucleotidekinase. Radiolabelled material is obtained from New England Nuclear(Boston, Mass.). The 10 microliter mixture is incubated at 37° C. forone hour. A 1 microliter aliquot of the mixture is chromatographed onDEAE paper (DE81 from Whatman) in 0.35 M ammonium bicarbonate. Thecounts that remain at the origin are used to determine the concentrationof the synthetic DNA.

Recombinant DNA methods

Isolation of plasmid DNA from E. coli cultures was performed asdescribed (Birnboim and Doly, 1979). Some DNAs were purified by Magic™miniprep columns, available from Promega (Madison, Wis.).

Purified plasmid DNA was treated with restriction endonucleasesaccording to manufacturer's instructions. Analysis of the DNA fragmentsproduced by treatment with restriction enzymes was done by agarose orpolyacrylamide gel electrophoresis. Agarose (DNA grade from Fisher,Pittsburgh Pa.) was used at a concentration of 1.0% in a Tris-acetaterunning buffer (0.04 M Tris-acetate, 0.001M EDTA). Polyacrylamide(BioRad, Richmond Calif.) was used at a concentration of 6% (19:1crosslinked) in 0.5× Tris-borate buffer (0.045 M Tris, 0.045 M boricacid, 1.25 mM EDTA), hereafter referred to as PAGE.

DNA polymerase I, large fragment, Klenow enzyme was used according tomanufacturer's instructions to catalyze the addition of mononucleotidesfrom 5' to 3' of DNA fragments which had been treated with restrictionenzymes that leave protruding ends. The reactions were incubated at 65°C. for 10 minutes to heat inactivate the Klenow enzyme.

The synthetic oligonucleotides were made without 5' or 3' terminalphosphates. In cases where such oligonucleotides were ligated end toend, the oligonucleotides were treated at a concentration of 10picomoles per microliter with T4 polynucleotide kinase in the followingbuffer: 25 mM Tris, pH 8.0, 10 mM MgCl₂, 10 mM dithiothreitol, 2 mMspermidine, 1 mM rATP. After incubation for 30 minutes at 37° C., thesamples were incubated at 65° C. for five minutes to heat inactivate thekinase.

Synthetic gene assembly

The (15-125) hIL-3 gene was divided into four regions separated by fiveconvenient restriction sites. In each of the four regions syntheticoligonucleotides were designed so that they would anneal incomplementary pairs, with protruding single stranded ends "or bluntends" and when the pairs were properly assembled would result in a DNAsequence that encoded a portion of the hIL-3 gene. Amino acidsubstitutions in the hIL-3 gene were made by designing theoligonucleotides to encode the desired substitutions. The complementaryoligonucleotides were annealed at concentration of 1 picomole permicroliter in ligation buffer plus 50 mM NaCl. The samples were heatedin a 100 ml beaker of boiling water and permitted to cool slowly to roomtemperature. One picomole of each of the annealed pairs ofoligonucleotides were ligated with approximately 0.2 picomoles ofplasmid DNA, digested with the appropriate restriction enzymes, inligation buffer (25 mM Tris pH 8.0, 10 mM MgCl₂, 10 mM dithiothreitol, 1mM ATP, 2mM spermidine) with T4 DNA ligase obtained from New EnglandBiolabs (Beverly, Mass.) in a total volume of 20 μl at room temperatureovernight.

DNA fragments were isolated from agarose gels by intercepting therestriction fragments on DEAE membranes from Schleicher and Schuell(Keene, N.H.) and eluting the DNA in 10 mM Tris, 1 mM EDTA, 1 M NaCl at55° C. for 1 hour, according to manufacturer's directions. The solutionscontaining the DNA fragment were concentrated and desalted by usingCentricon 30 concentrators from Amicon (W. R. Grace, Beverly Mass.)according to the manufacturer's directions. Ligations were performed at15° C. overnight, except as noted, in ligation buffer (66 mM Tris pH7.5, 6.6 mM MgCl₂, 1 mM dithiothreitol, 0.4 mM ATP) with T₄ ligaseobtained from New England Biolabs (Beverly, Mass.).

Polymerase Chain Reaction

Polymerase Chain Reaction (hereafter referred to as PCR) techniques(Saiki, 1985) used the reagent kit and thermal cycler from Perkin-ElmerCetus (Norwalk, Conn.). PCR is based on a thermostable DNA polymerasefrom Thermus aquaticus. The PCR technique is a DNA amplification methodthat mimics the natural DNA replication process in that the number ofDNA molecules doubles after each cycle, in a way similar to in vivoreplication. The DNA polymerase mediated extension is in a 5'→43'direction. The term "primer" as used herein refers to an oligonucleotidesequence that provides an end to which the DNA polymerase can addnucleotides that are complementary to a nucleotide sequence. The latternucleotide sequence is referred to as the "template", to which theprimers are annealed. The amplified PCR product is defined as the regioncomprised between the 5' ends of the extension primers. Since theprimers have defined sequences, the product will have discrete ends,corresponding to the primer sequences. The primer extension reaction wascarried out using 20 picomoles (pmoles) of each of the oligonucleotidesand 1 picogram of template plasmid DNA for 35 cycles (1 cycle is definedas 94° C. for one minute, 50° C. for two minutes and 72° C. for threeminutes). The reaction mixture was extracted with an equal volume ofphenol/chloroform (50% phenol and 50% chloroform, volume to volume) toremove proteins. The aqueous phase, containing the amplified DNA, andsolvent phase were separated by centrifugation for 5 minutes in amicrocentrifuge (Model 5414 Eppendorf Inc, Fremont Calif.). Toprecipitate the amplified DNA the aqueous phase was removed andtransferred to a fresh tube to which was added 1/10 volume of 3M NaOAc(pH 5.2) and 2.5 volumes of ethanol (100% stored at minus 20° C.). Thesolution was mixed and placed on dry ice for 20 minutes. The DNA waspelleted by centrifugation for 10 minutes in a microcentrifuge and thesolution was removed from the pellet. The DNA pellet was washed with 70%ethanol, ethanol removed and dried in a speedvac concentrator (Savant,Farmingdale, N.Y.). The pellet was resuspended in 25 microliters of TE(20 mM Tris-HCl pH 7.9, 1 mM EDTA). Alternatively the DNA wasprecipitated by adding equal volume of 4M NH₄ OAc and one volume ofisopropanol [Treco, (1989)]. The solution was mixed and incubated atroom temperature for 10 minutes and centrifuged. These conditionsselectively precipitate DNA fragments larger than ˜20 bases and wereused to remove oligonucleotide primers. One quarter of the reaction wasdigested with restriction enzymes [Higuchi, (1989)] and on completionheated to 70° C. to inactivate the enzymes.

Two step site-directed PCR mutagenesis

Single amino acid substitution variants were created at positions 17-123of hIL-3 in two site-directed mutagenesis steps by PCR (Bauer et al.manuscript in preparation).

The single amino acid substitution variants at positions 94-105 of hIL-3were created as described below. In the first mutagenesis step plasmidDNA, containing the hIL-3 gene (amino acids 15-125), was the template inthe PCR reaction. The DNA sequence of one of the oligonucleotide primerswas designed to replace 12 base in the hIL-3 gene (15-125) with 12 basesencoding two translation stop codons (5'TAATAA3'), followed by therecognition sequence (5'GTCGAC3') restriction enzyme SalI. This 12 basesequence was substituted in the hIL-3 gene following the codon for aminoacids 93, 97 and 101. Plasmids containing these mutagenized genes servedas the templates for the second mutagenesis step.

In the second mutagenesis step, the 12 base substitution introduced inthe first mutagenesis step, was replaced using a 32 fold degenerateoligonucleotide. The degenerate oligonucleotides were synthesized bymachine mixing an equal molar ratio of the desired nucleosides in thecondensation reaction at degenerate positions. The degenerateoligonucleotides have G, A, T or C in the first and second positions andG or C in the third position of a single codon. The other bases in theoligonucleotides corresponded to the hIL-3 sequence. The degenerateoligonucleotides theoretically contain 32 different codons, encoding all20 amino acids and one translation stop codon, at a single position. Atthe other 9 bases the DNA sequence was restored to encode the nativehIL-3 protein sequence. This pool of single amino acid substitutions ata single position is referred to as a "library". This two step PCRsite-directed mutagenesis approach was used to facilitate theidentification of single amino acid substitution variants bydifferential DNA hybridization.

The single amino acid substitution variants at positions 17-93 and106-123 of hIL-3 (15-125) were created as described below. In the firstmutagenesis step plasmid DNA, containing the hIL-3 gene (15-125), wasthe template in the PCR reaction. The DNA sequence of one of theoligonucleotide primers was designed to delete 18 bases in the hIL-3gene that encode the following amino acids; 17-22, 23-28, 29-34, 35-40,41-46, 47-52, 53-58, 59-64, 65-70, 71-76, 77-82, 83-88, 88-93, 106-111,112-117 and 118-123. Plasmids containing these deletion genes served asthe templates for the second mutagenesis step.

In the second mutagenesis step the 18 base deletion, created in thefirst mutagenesis step, was restored using a 32 fold degenerateoligonucleotide. The degenerate oligonucleotides have G, A, T or C inthe first and second positions and G or C in the third position of asingle codon. The other bases in the oligonucleotides corresponded tothe hIL-3 sequence. The degenerate oligonucleotides theoreticallycontain 32 different codons, encoding all 20 amino acids and onetranslation stop codon, at a single position. At the other 9 bases theDNA sequence was restored to encode the native hIL-3 protein sequence.This pool of single amino acid substitutions at a single position isreferred to as a "library". This two step PCR site-directed mutagenesisapproach was used to facilitate the identification of single amino acidsubstitution variants by differential DNA hybridization.

Recovery of recombinant plasmids from ligation mixes and transformationof E. coli cells with recombinant plasmid DNA

E. coli JM101 cells were made competent to take up DNA. Typically, 20 to100 ml of cells were grown in LB medium to a density of approximately150 Klett units and then collected by centrifugation. The cells wereresuspended in one half culture volume of 50 mM CaCl₂ and held at 4° C.for one hour. The cells were again collected by centrifugation andresuspended in one tenth culture volume of 50 mM CaCl₂. DNA was added toa 150 microliter volume of these cells, and the samples were held at 4°C. for 30 minutes. The samples were shifted to 42° C. for one minute,one milliliter of LB was added, and the samples were shaken at 37° C.for one hour. Cells from these samples were spread on plates containingampicillin to select for transformants. The plates were incubatedovernight at 37° C. Single colonies were picked and grown in LBsupplemented with ampicillin overnight at 37° C. with shaking. Fromthese cultures DNA was isolated for restriction analysis.

Typically plasmids were constructed, using methods described herein orby references cited herein, as follows except as noted in examplesincluded herein. DNA fragments were purified from agarose orpolyacrylamide gels. Purified DNA fragments were ligated and theligation reaction mixture was used to transform E. coli K-12 strainJM101. Transformant bacteria were selected on ampicillin containingplates. Plasmid DNA was isolated from a single colony grown in LB Brothand screened by restriction analysis for the desired construct andsequenced to determine that the DNA sequence was correct.

Culture media

LB medium (Maniatis et al., 1982) was used for growth of cells for DNAisolation. M9 minimal medium supplemented with 1.0% casamino acids, acidhydrolyzed casein, Difco (Detroit, Mich.) was used for cultures in whichrecombinant hIL-3 was produced. The ingredients in the M9 medium were asfollows: 3 g/liter KH₂ PO₄, 6 g/l Na₂ HPO₄, 0.5 g/l NaCl, 1 g/l NH₄ Cl,1.2 mM MgSO₄, 0.025 mM CaCl₂, 0.2% glucose (0.2% glycerol with theAraBAD promoter), 1% casamino acids, 0.1 ml/l trace minerals (per liter108 g FeCl₃.6H₂ O, 4.0 g ZnSO₄.7H₂ O, 7.0 CoCl₂.2H₂ O, 7.0 g Na₂MoO₄.2H₂ O, 8.0 g CuSO₄.5H₂ O, 2.0 g H₃ BO₃, 5.0 g MnSO₄.H₂ O, 100 mlconcentrated HCl). Bacto agar from Difco was used for solid media andampicillin (Polycillin-N from Bristol-Meyers, Evansville, Ind.) wasadded to both liquid and solid LB media at 200 micrograms permilliliter.

DNA sequence analysis

The nucleotide sequencing of plasmid DNA was performed using a Genesis2000 sequencer obtained from DuPont (Wilmington, Del.) according to themethods of Prober et al. (1987) and Sanger et al. (1977). Some DNAsequences were determined using Sequenase™ polymerase according to theprotocol of its supplier, U.S. Biochemicals (Cleveland, Ohio).

Production of recombinant hIL-3 muteins in E. coli with vectorsemploying the recA promoter

E. coli strains harboring the plasmids of interest were grown at 37° C.in M9 plus casamino acids medium with shaking in a Gyrotory water bathModel G76 from New Brunswick Scientific (Edison, N.J.). Growth wasmonitored with a Klett Summerson meter (green 54 filter), Klett Mfg. Co.(New York, N.Y.). At a Klett value of approximately 150, an aliquot ofthe culture (usually one milliliter) was removed for protein analysis.To the remaining culture, nalidixic acid (10 mg/ml) in 0.1 N NaOH wasadded to a final concentration of 50 μg/ml. The cultures were shaken at37° C. for three to four hours after addition of nalidixic acid. A highdegree of aeration was maintained throughout the bacterial growth inorder to achieve maximal production of the desired gene product. Thecells were examined under a light microscope for the presence ofretractile bodies (RBs). One milliliter aliquots of the culture wereremoved for analysis of protein content.

Production of recombinant hIL-3 proteins from the AraBAD promoter in E.coli

E. coli strains harboring the plasmids of interest were grown at 30° C.with shaking in M9 medium plus casamino acids and glycerol. Growth wasmonitored with a Klett Summerson calorimeter, using a green 54 filter.At a Klett value of about 150, an aliquot of the culture (usually onemilliliter) was removed for protein analysis. To the remaining culture,20% arabinose was added to a final concentration of 0.05%. The cultureswere shaken at 30° C. for three to four hours after addition ofarabinose. A high degree of aeration was maintained throughout thebacterial growth in order to achieve maximal production of the desiredgene product. One milliliter aliquots of the culture were removed foranalysis of protein content.

Secretion and osmotic shock

Three hour post induction samples were fractionated by osmotic shock[Neu and Heppel (1965)]. The Klett value of the cultures was determinedand 1 ml of cells were centrifuged in a Sigma microcentrifuge (WestGermany) model 202MK in 1.5 mls snap top microcentrifuge tubes for 5minutes at 10,000 rpm. The cell pellet was resuspended very gently bypipeting in a room temperature sucrose solution (20% sucrose w/v, 30 mMTris-Hcl pH7.5, 1 mM EDTA), using 1 μl/1 Klett unit. Following a 10minute incubation at room temperature, the cells were centrifuged for 5minutes at 10,000 rpm. The sucrose fraction was carefully removed fromthe cell pellet. The cell pellet was then resuspended very gently bypipeting in ice cold distilled water, using 1 μl/1 Klett unit. Followinga 10 minute incubation on ice, the cells were centrifuged for 5 minutesat 12,000 rpm. The water fraction was carefully removed. Equal volumesof the sucrose and water fractions were pooled and aliquoted to providesamples for ELISA and biological activity screening.

Analysis of protein content of E. coli cultures producing hIL-3 mutantpolypeptides

Bacterial cells from cultures treated as described above were collectedfrom the medium by centrifugation. Aliquots of these cells wereresuspended in SDS loading buffer (4×: 6 g SDS, 10 mlbeta-mercaptoethanol, 25 ml upper Tris gel stock (0.5 M Tris HCl pH 6.8,0.4% SDS) brought to 50 ml with glycerol, 0.2% bromophenol blue wasadded) at a concentration of one microliter per Klett unit. Thesesamples were incubated at 85° C. for five minutes and vortexed. Five orten microliter aliquots of these samples were loaded on 15%polyacrylamide gels prepared according to the method of Laemmli (1970).Protein bands were visualized by staining the gels with a solution ofacetic acid, methanol and water at 5:1:5 (volume to volume) ratio towhich Coomassie blue had been added to a final concentration of 1%.After staining, the gels were washed in the same solution without theCoomassie blue and then washed with a solution of 7% acetic acid, 5%methanol. Gels were dried on a gel drier Model SE1160 obtained fromHoeffer (San Francisco, Calif.). The amount of stained protein wasmeasured using a densitometer obtained from Joyce-Loebl (Gateshead,England). The values obtained were a measure of the amount of thestained hIL-3 protein compared to the total of the stained protein ofthe bacterial cells.

Western blot analysis of hIL-3 muteins made in E. coli

In some E. coli cultures producing hIL-3, the level of accumulation ofthe hIL-3 protein is lower than 5% of total bacterial protein. To detecthIL-3 produced at this level, Western blot analysis was used. Proteinsfrom cultures induced with nalidixic acid or arabinose were run onpolyacrylamide gels as described above except that volumes of sampleloaded were adjusted to produce appropriate signals. Afterelectrophoresis, the proteins were electroblotted to APT paper,Transa-bind, Schleicher and Schuell (Keene, N.H.) according to themethod of Renart et al. (1979). Antisera used to probe these blots hadbeen raised in rabbits, using peptides of the sequence of amino acids 20to 41 and 94 to 118 of hIL-3 as the immunogens. The presence of boundantibody was detected with Staphylococcal protein A radiolabeled with¹²⁵ I, obtained from New England Nuclear (Boston, Mass.).

Fractionation of E. coli cells producing hIL-3 proteins in the cytoplasm

Cells from E. coli cultures harboring plasmids that produce hIL-3muteins were induced with nalidixic acid. After three hours, the hIL-3muteins accumulated in refractile bodies. The first step in purificationof the hIL-3 muteins was to sonicate cells. Aliquots of the culture wereresuspended from cell pellets in sonication buffer: 10 mM Tris, pH 8.0,1 mM EDTA, 50 mM NaCl and 0.1 mM PMSF. These resuspended cells weresubjected to several repeated sonication bursts using the microtip froma Sonicator cell disrupter, Model W-375 obtained from HeatSystems-Ultrasonics Inc. (Farmingdale, N.Y.). The extent of sonicationwas monitored by examining the homogenates under a light microscope.When nearly all of the cells had been broken, the homogenates werefractionated by centrifugation. The pellets, which contain most of therefractile bodies, are highly enriched for hIL-3 muteins.

Methods: Extraction, Refolding and Purification of Interleukin-3 (IL-3)Muteins Expressed as Refractile Bodies in E. coli

For each gram of RB's (and typically one gram is obtained from a 300 mlE. coli culture), 5 ml of a solution containing 6M guanidinehydrochloride (GnHCl), 50 mM 2-N-cyclohexylaminoethanesulfonic acid(CHES) pH 9.5 and 20 mM dithiothreitol (DTT) was added. The RB's wereextracted with a Bio-Homogenizer for 15-30 seconds and gently rocked for2 hours at 5 degrees centigrade (5° C.) to allow the protein tocompletely reduce and denature.

Refolding of the IL-3 muteins

The protein solution was transferred to dialysis tubing (1000 molecularweight cut-off) and dialyzed against at least 100 volumes of 4MGnHCl--50 mM CHES pH 8.0. The dialysis was continued overnight at 5° C.while gently stirring. Subsequently dialysis was continued against atleast 100 volumes of 2M GnHCl--50 mM CHES pH 8.0 and dialyzed overnightat 5° C. while gently stirring.

Purification of the IL-3 muteins

The protein solution was removed from the dialysis tubing and acidifiedby the addition of 40% acetonitrile (CH₃ CN)--0.2% trifluoroacetic acid(TFA) to a final concentration of 20% CH₃ CN--0.1% TFA. This wascentrifuged (16,000×g for 5 minutes) to clarify and the supernatant wasloaded onto a Vydac C-18 reversed phase column (10×250 mm) availablefrom Vydac (Hesperia, Calif.) previously equilibrated in 20% CH₃CN--0.1% TFA. The column was eluted with a linear gradient (0.2% CH₃CN/minute) between 40-50% CH₃ CN--0.1% TFA at a flow rate of 3 ml/minutewhile collecting 1.5 ml fractions. The fractions were analyzed bypolyacrylamide gel electrophoresis (SDS-PAGE) and the appropriatefractions pooled. The pooled material was dried by lyophilization or ina Speed Vac concentrator. The dry powder was reconstituted with 10 mMammonium bicarbonate pH 7.5, centrifuged (16,000×g for 5 minutes) toclarify and assayed for protein concentration by the method of Bradford(1976) with bovine serum albumin as the standard. Such protein can befurther analyzed by additional techniques such as, SDS-PAGE,electrospray mass spectrometry, reverse phase HPLC, capillary zoneelectrophoresis, amino acid composition analysis, and ELISA(enzyme-linked immunosorbent assay).

hIL-3 SANDWICH ELISA

IL-3 protein concentrations were determined using a sandwich ELISA basedon an affinity purified polyclonal goat anti-rhIL-3. Microtiter plates(Dynatech Immulon II) were coated with 150 μl goat-anti-rhIL-3 at aconcentration of approximately 1 μg/ml in 100 mM NaHCO3, pH 8.2. Plateswere incubated overnight at room temperature in a chamber maintaining100% humidity. Wells were emptied and the remaining reactive sites onthe plate were blocked with 200 μl of solution containing 10 mM PBS, 3%BSA and 0.05% Tween 20, pH 7.4 for 1 hour at 37° C. and 100% humidity.Wells were emptied and washed 4× with 150 mM NaCl containing 0.05% Tween20 (wash buffer). Each well then received 150 μl of dilution buffer (10mM PBS containing 0.1% BSA, 0.01% Tween 20, pH 7.4), containing rhIL-3standard, control, sample or dilution buffer alone. A standard curve wasprepared with concentrations ranging from 0.125 ng/ml to 5 ng/ml using astock solution of rhIL-3 (concentration determined by amino acidcomposition analysis). Plates were incubated 2.5 hours at 37° C. and100% humidity. Wells were emptied and each plate was washed 4× with washbuffer. Each well then received 150 μl of an optimal dilution (asdetermined in a checkerboard assay format) of goat anti-rhIL-3conjugated to horseradish peroxidase. Plates were incubated 1.5 hours at37° C. and 100% humidity. Wells were emptied and each plate was washed4× with wash buffer. Each well then received 150 ul of ABTS substratesolution (Kirkegaard and Perry). Plates were incubated at roomtemperature until the color of the standard wells containing 5 ng/mlrhIL-3 had developed enough to yield an absorbance between 0.5-1.0 whenread at a test wavelength of 410 nm and a reference wavelength of 570 nmon a Dynatech microtiter plate reader. Concentrations of immunoreactiverhIL-3 in unknown samples were calculated from the standard curve usingsoftware supplied with the plate reader.

AML Proliferation Assay for Bioactive Human Interleukin-3

The factor-dependent cell line AML 193 was obtained from the AmericanType Culture Collection (ATCC, Rockville, Md.). This cell line,established from a patient with acute myelogenous leukemia, is a growthfactor dependent cell line which displayed enhanced growth in GM/CSFsupplemented medium (Lange, B., et al., (1987); Valtieri, M., et al.,(1987). The ability of AML 193 cells to proliferate in the presence ofhuman IL-3 has also been documented. (Santoli, D., et al., (1987)). Acell line variant was used, AML 193 1.3, which was adapted for long termgrowth in IL-3 by washing out the growth factors and starving thecytokine dependent AML 193 cells for growth factors for 24 hours. Thecells were then replated at 1×10⁵ cells/well in a 24 well plate in mediacontaining 100 U/ml IL-3. It took approximately 2 months for the cellsto grow rapidly in IL-3. These cells were maintained as AML 193 1.3thereafter by supplementing tissue culture medium (see below) with humanIL-3.

AML 193 1.3 cells were washed 6 times in cold Hanks balanced saltsolution (HBSS, Gibco, Grand Island, N.Y.) by centrifuging cellsuspensions at 250×g for 10 minutes followed by decantation ofsupernatant. Pelleted cells were resuspended in HBSS and the procedurewas repeated until six wash cycles were completed. Cells washed sixtimes by this procedure were resuspended in tissue culture medium at adensity ranging from 2×10⁵ to 5×10⁵ viable cells/ml. This medium wasprepared by supplementing Iscove's modified Dulbecco's Medium (IMDM,Hazleton, Lenexa, Kans.) with albumin, transferrin, lipids and2-mercaptoethanol. Bovine albumin (Boehringer-Mannheim, Indianapolis,Ind.) was added at 500 μg/ml; human transferrin (Boehringer-Mannheim,Indianapolis, Ind.) was added at 100 μg/ml; soybean lipid(Boehringer-Mannheim, Indianapolis, Ind.) was added at 50 μg/ml; and2-mercaptoethanol (Sigma, St. Louis, Mo.) was added at 5×10⁻⁵ M.

Serial dilutions of human interleukin-3 or human interleukin-3 variantprotein (hIL-3 mutein) were made in triplicate series in tissue culturemedium supplemented as stated above in 96 well Costar 3596 tissueculture plates. Each well contained 50 μl of medium containinginterleukin-3 or interleukin-3 variant protein once serial dilutionswere completed. Control wells contained tissue culture medium alone(negative control). AML 193 1.3 cell suspensions prepared as above wereadded to each well by pipetting 50 μl (2.5×10⁴ cells) into each well.Tissue culture plates were incubated at 37° C. with 5% CO₂ in humidifiedair for 3 days. On day 3, 0.5 μCi ³ H-thymidine (2 Ci/mM, New EnglandNuclear, Boston, Mass.) was added in 50 μl of tissue culture medium.Cultures were incubated at 37° C. with 5% CO₂ in humidified air for18-24 hours. Cellular DNA was harvested onto glass filter mats(Pharmacia LKB, Gaithersburg, Md.) using a TOMTEC cell harvester(TOMTEC, Orange, Conn.) which utilized a water wash cycle followed by a70% ethanol wash cycle. Filter mats were allowed to air dry and thenplaced into sample bags to which scintillation fluid (Scintiverse II,Fisher Scientific, St. Louis, Mo. or BetaPlate Scintillation Fluid,Pharmacia LKB, Gaithersburg, Md.) was added. Beta emissions of samplesfrom individual tissue culture wells were counted in a LKB Betaplatemodel 1205 scintillation counter (Pharmacia LKB, Gaithersburg, Md.) anddata was expressed as counts per minute of ³ H-thymidine incorporatedinto cells from each tissue culture well. Activity of each humaninterleukin-3 preparation or human interleukin-3 variant preparation wasquantitated by measuring cell proliferation (³ H-thymidineincorporation) induced by graded concentrations of interleukin-3 orinterleukin-3 variant. Typically, concentration ranges from 0.05 pM-10⁵pM are quantitated in these assays. Activity is determined by measuringthe dose of interleukin-3 or interleukin-3 variant which provides 50% ofmaximal proliferation [EC₅₀ =0.5×(maximum average counts per minute of ³H-thymidine incorporated per well among triplicate cultures of allconcentrations of interleukin-3 tested--background proliferationmeasured by ³ H-thymidine incorporation observed in triplicate cultureslacking interleukin-3]. This EC₅₀ value is also equivalent to 1 unit ofbioactivity. Every assay was performed with native interleukin-3 as areference standard so that relative activity levels could be assigned.

Relative biological activities of some IL-3 muteins of the presentinvention are shown in Table 1. The Relative Biological Activity of IL-3mutants is calculated by dividing the EC₅₀ of (1-133) hIL-3 by the EC50of the mutant. The Relative Biological Activity may represent theaverage of replicate assays.

                  TABLE 1                                                         ______________________________________                                        BIOLOGICAL ACTIVITY OF IL-3 MUTEINS                                                                         Relative                                                                       Plasmid Polypeptide Biological                   Code Structure Activity                                                     ______________________________________                                        Reference     (1-133) hIL-3                                                                             1.0                                                   pMON13286 [SEQ ID NO. 69] 8.0                                                 pMON13304 [SEQ ID NO. 66] 3.2                                               ______________________________________                                         *The Relative Biological Activity of IL3 mutants is calculated by dividin     the EC.sub.50 of (1-133) hIL3 by the EC.sub.50 of the mutant.            

The following assay is used to measure IL-3 mediated sulfidoleukotrienerelease from human mononuclear cells.

IL-3 mediated sulfidoleukotriene release from human mononuclear cells

Heparin-containing human blood was collected and layered onto an equalvolume of Ficoll-Paque (Pharmacia #17-0840-02) ready to use medium(density 1.077 g/ml.). The Ficoll was warmed to room temperature priorto use and clear 50 ml polystyrene tubes were utilized. The Ficollgradient was spun at 300×g for 30 minutes at room temperature using aH1000B rotor in a Sorvall RT6000B refrigerated centrifuge. The bandcontaining the mononuclear cells was carefully removed, the volumeadjusted to 50 mls with Dulbecco's phosphate-buffered saline (GibcoLaboratories cat. #310-4040PK), spun at 400×g for 10 minutes at 4° C.and the supernatant was carefully removed. The cell pellet was washedtwice with HA Buffer [20 mM Hepes (Sigma #H-3375), 125 mM NaCl (Fisher#S271-500), 5 mM KCl (Sigma #P-9541), 0.5 mM glucose (Sigma#G-5000),0.025% Human Serum Albumin (Calbiochem #126654) and spun at300×g, 10 min., 4° C. The cells were resuspended in HACM Buffer (HAbuffer supplemented with 1 mM CaCl₂ (Fisher #C79-500) and 1 mM MgCl₂(Fisher #M-33) at a concentration of 1×106 cells/ml and 180 μl weretransferred into each well of 96 well tissue culture plates. The cellswere allowed to acclimate at 37° C. for 15 minutes. The cells wereprimed by adding 10 μls of a 20× stock of various concentrations ofcytokine to each well (typically 100000, 20000, 4000, 800, 160, 32, 6.4,1.28, 0 fM IL3). The cells were incubated for 15 minutes at 37° C.Sulfidoleukotriene release was activated by the addition of 10 μls of20× (1000 nM) fmet-leu-phe (Calbiochem #344252) final concentration 50nMFMLP and incubated for 10 minutes at 37° C. The plates were spun at350×g at 4° C. for 20 minutes. The supernatants were removed and assayedfor sulfidoleukotrienes using Cayman's Leukotriene C4 EIA kit (Cat.#420211) according to manufacturers' directions. Native (15-125)hIL-3was run as a standard control in each assay.

Native hIL-3 possesses considerable inflammatory activity and has beenshown to stimulate synthesis of the arachidonic acid metabolites LTC₄,LTD₄, and LTE₄ ; histamine synthesis and histamine release. Humanclinical trials with native hIL-3 have documented inflammatory responses(Biesma, et al., BLOOD, 80:1141-1148 (1992) and Postmus, et al., J.CLIN. ONCOL., 10:1131-1140 (1992)). A recent study indicates thatleukotrienes are involved in IL-3 actions in vivo and may contributesignificantly to the biological effects of IL-3 treatment (Denzlinger,C., et al., BLOOD, 81:2466-2470 (1993)),

Some muteins of the present invention may have an improved therapeuticprofile as compared to native hIL-3 or (15-125)hIL-3. For example, somemuteins of the present invention may have a similar or more potentgrowth factor activity relative to native hIL-3 or (15-125)hIL-3 withouthaving a similar or corresponding increase in the stimulation ofleukotriene or histamine. These muteins would be expected to have a morefavorable therapeutic profile since the amount of polypeptide whichneeds to be given to achieve the desired growth factor activity (e. g.cell proliferation) would have a lesser leukotriene or histaminestimulating effect. In studies with native hIL-3, the stimulation ofinflammatory factors has been an undesirable side effect of thetreatment. Reduction or elimination of the stimulation of mediators ofinflammation would provide an advantage over the use of native hIL-3.

Some muteins of the present invention may have antigenic profiles whichdiffer from that of native hIL-3. For example, in a competition ELISAwith an affinity purified polyclonal goat anti-hIL-3 antibody, nativehIL-3 significantly blocked the binding of labeled hIL-3 to polyclonalanti-hIL-3 antibody. Some polypeptides of the present invention,particularly those with several amino acids differing from those ofnative hIL-3, fail to block the binding of hIL-3 to anti-hIL-3 antibody.

Table 2 lists the sequences of some oligonucleotides used in making themuteins of the present invention.

Table 3 lists the amino acid sequence of native (15-125)hIL-3 (Peptide#1) and the amino acid sequences of some mutant polypeptides of thepresent invention. The sequences are shown with the amino acid numberingcorresponding to that of native hIL-3 [FIG. 1].

                                      TABLE 2                                     __________________________________________________________________________    OLIGONUCLEOTIDES                                                              __________________________________________________________________________    Oligo #1                                                                         - AATTCCGTCG TAAACTGACC TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAGT                                                [SEQ ID NO:8]                            - AATA                                                                        - Oligo #2                                                                    - AGCTTATTAC TGTTGAGCCT GCGCGTTCTC CAAGGTTTTC AGATAGAAGG TCAGTTTACG                                                [SEQ ID NO:9]                            - ACGG                                                                        - Oligo #3                                                                    - CTAGCCACGG CCGCACCCAC GCGACATCCA ATCCATATCA AGGACGGTGA CTGGAATG [SEQ                                             ID NO:24]                                - Oligo #4                                                                    - TTAACATTCC AGTCACCGTC CTTGATATGG ATTGGATGTC GCGTGGGTGC GGCCGTGG [SEQ                                             ID NO:25]                                - Oligo #5                                                                    - CATGGCTAAC TGCTCTAACA TGAT [SEQ ID NO:151]                                  - Oligo #6                                                                    - CGATCAT GTTAGAGCAGTTAGC [SEQ ID NO:152]                                     - Oligo #7 IL3MUTNCO                                                          - TGTCTGCTCA GGCCATGGCT [SEQ ID NO:26]                                        - Oligo #8 IL3T93                                                             - GCGCGAATTC ATTCCAGTCA CCGTCCTTGA TATGGTCGAC TTATTACGTG GGTGCGGCCG                                                [SEQ ID NO:27]                           - TGGCTAG                                                                     - Oligo #9 IL3T97                                                             - GCGCGAATTC ATTCCAGTCA CCGTCGACTT ATTAGATTGG ATGTCGCGTG GGTGC [SEQ ID                                             NO:28]                                   - Oligo #10 IL3T101                                                           - GCGCGAATTC GTCGACTTAT TAGTCCTTGA TATGGATTGG ATG [SEQ ID NO:31]                                                     - Oligo #11 IL3R94                     - GCGCGAATTC ATTCCAGTCA CCGTCCTTGA TATGGATTGG ATGSNNCGTG GGTGCGGCCG                                                [SEQ ID NO:32]                           - TGGCTAG                                                                     - Oligo #12 IL3R95                                                            - GCGCGAATTC ATTCCAGTCA CCGTCCTTGA TATGGATTGG SNNTCGCGTG GGTGCGGCCG                                                [SEQ ID NO:33]                           - TGGC                                                                        - Oligo #13 IL3R96                                                            - GCGCGAATTC ATTCCAGTCA CCGTCCTTGA TATGGATSNN ATGTCGCGTG GGTGCGGCCG                                                [SEQ ID NO:34]                           - T                                                                           - Oligo #14 IL3R97                                                            - GCGCGAATTC ATTCCAGTCA CCGTCCTTGA TATGSNNTGG ATGTCGCGTG GGTGCGGC [SEQ                                             ID NO:35]                                - Oligo #15 IL3P9497                                                          - GATATGGATT GGATGTCGCG TGGG [SEQ ID NO:36]                                   - Oligo #16 IL3R98                                                            - GCGCGAATTC ATTCCAGTCA CCGTCCTTGA TSNNGATTGG ATGTCGCGTG GGTGC [SEQ ID                                             NO:37]                                   - Oligo #17 IL3R99                                                            - GCGCGAATTC ATTCCAGTCA CCGTCCTTSN NATGGATTGG ATGTCGCGTG GG [SEQ ID                                                NO:38]                                   - Oligo #18 IL3R100                                                           - GCGCGAATTC ATTCCAGTCA CCGTCSNNGA TATGGATTGG ATGTCGCGT [SEQ ID NO:39]        - Oligo #19 IL3R101                                                           - GCGCGAATTC ATTCCAGTCA CCSNNCTTGA TATGGATTGG ATGTCG [SEQ ID NO:40]                                                  - Oligo #20 IL3P98100                  - GTCACCGTCC TTGATATGGA TTGG [SEQ ID NO:41]                                   - Oligo #21 IL3R102                                                           - GCGCGAATTC ATTCCAGTCS NNGTCCTTGA TATGGATTGG ATG [SEQ ID NO:42]                                                     - Oligo #22 IL3R103                    - GCGCGAATTC ATTCCASNNA CCGTCCTTGA TATGGATTGG [SEQ ID NO:43]                  - Oligo #23 IL3R104                                                           - GCGCGAATTC ATTSNNGTCA CCGTCCTTGA TATGGAT [SEQ ID NO:44]                     - Oligo #24 IL3R105                                                           - GCGCGAATTC SNNCCAGTCA CCGTCCTTGA TATG [SEQ ID NO:45]                        - Oligo #25 IL3P102105                                                        - GAATTCATTC CAGTCACCGT TCCTT [SEQ ID NO:46]                                  - Oligo #26 IL3MUTR1                                                          - CGCGCGGAAT TCATTCCAGT CACCGT [SEQ ID NO:47]                                 - Oligo #27 DEL1722                                                           - CGCGCGCCAT GGCTAACTGC ATTATAACAC ACACTTAAAG CA [SEQ ID NO:48]                                                      - Oligo #28 DEL2328                    - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAACA GCCACCTTTG CCTTTGCT [SEQ                                             ID NO:49]                                - Oligo #29 DEL2934                                                           - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TATAACACAC TTAAAGCTGG                                                [SEQ ID NO:50]                           - ACTTCAACAA CCTCAA                                                           - Oligo #30 DEL3540                                                           - GCGCGCGATA TCTTGGTCTT CTTCACCATT CAGCGGCAGC GGTGGCTGCT [SEQ ID                                                   NO:51]                                   - Oligo #31 DEL4146                                                           - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT ATTTTCCATC AGGATGAGGT TGTTGAAGTC                                                [SEQ ID NO:52]                           - CAGCA                                                                       - Oligo #32 DEL4752                                                           - GCGCGCCTCG AGGTTTGGAC GACGAAGATC TTGGTCTTCA CCATTGA [SEQ ID NO:53]                                                 - Oligo #33 DEL5358                    - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCACGGTTG AATGCCTCGT TATTTTCCAT                                                [SEQ ID NO:54]                           - CAGGATAT                                                                    - Oligo #34 DEL5964                                                           - GCGCGCTGAT GCATTCTGCA GAGACTTGAC GAGGTTTGGA CGACGAAGGT [SEQ ID                                                   NO:55]                                   - Oligo #35 DEL6570                                                           - GCGCGCCTCG AGGCATTCAA CCGTGCTGCA TCAGCAATTG AGAGCAT [SEQ ID NO:56]                                                 - Oligo #36 DEL7176                    - GCGCGCCTGC AGAATATTCT TAAAAATCTC CTGCC [SEQ ID NO:57]                       - Oligo #37 DEL7782                                                           - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCCCATGTC TGCCGCTAGC CAC [SEQ ID                                               NO:58]                                   - Oligo #38 DEL8388                                                           - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTCTTA AAAATCTCCT GACGGCCGCA                                                [SEQ ID NO:59]                           - CCCACGCGAC A                                                                - Oligo #39 DEL8893                                                           - CGCGCGGAAT TCATTCCAGT CACCGTCCTT GATATGGATT GGATGTCGCA GGGCAGACAT                                                [SEQ ID NO:60]                           - GGCAGGA                                                                     - Oligo #40 DEL106111                                                         - CGCGCGAAGC TTATTACTGT TGAGCCTGCG CGTTCTCCAA GGTTTTCAGA TAGAAGGTAT                                                [SEQ ID NO:61]                           - TCCAGTCACC GTCCTTGA                                                         - Oligo #41 DEL112117                                                         - CGCGCGAAGC TTATTACTGT TGAGCCTGCG CGTTCTCCAA CAGTTTACGA CGGAATTCAT                                                [SEQ ID NO:62]                           - Oligo #42 DEL118123                                                         - CGCGCGAAGC TTATTACTGT TGGGTTTTCA GATAGAAGGT CA [SEQ ID NO:63]                                                      - Oligo #43 R17IL3 Length:                                                  000058                                   - CGCGCGCCAT GGCTAACTGC NNSAACATGA TCGATGAAAT TATAACACAC TTAAAGCA [SEQ                                             ID NO:64]                                - Oligo #44 R18IL3 Length: 000058                                             - CGCGCGCCAT GGCTAACTGC TCTNNSATGA TCGATGAAAT TATAACACAC TTAAAGCA [SEQ                                             ID NO:222]                               - Oligo #45 R19IL3 Length: 000058                                             - CGCGCGCCAT GGCTAACTGC TCTAACNNSA TCGATGAAAT TATAACACAC TTAAAGCA [SEQ                                             ID NO:223]                               - Oligo #46 R20IL3 Length: 000058                                             - CGCGCGCCAT GGCTAACTGC TCTAACATGN NSGATGAAAT TATAACACAC TTAAAGCA [SEQ                                             ID NO:224]                               - Oligo #47 R21IL3 Length: 000058                                             - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCNNSGAAAT TATAACACAC TTAAAGCA [SEQ                                             ID NO:225]                               - Oligo #48 R22IL3 Length: 000058                                             - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATNNSAT TATAACACAC TTAAAGCA [SEQ                                             ID NO:226]                               - Oligo #49 R23IL3 Length: 000076                                             - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAANN SATAACACAC TTAAAGCAGC                                                [SEQ ID NO:227]                          - CACCTTTGCC TTTGCT                                                           - Oligo #50 R24IL3 Length: 000076                                             - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TNNSACACAC TTAAAGCAGC                                                [SEQ ID NO:228]                          - CACCTTTGCC TTTGCT                                                           - Oligo #51 R25IL3 Length: 000076                                             - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TATANNSCAC TTAAAGCAGC                                                [SEQ ID NO:229]                          - CACCTTTGCC TTTGCT                                                           - Oligo #52 R26IL3 Length: 000076                                             - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TATAACANNS TTAAAGCAGC                                                [SEQ ID NO:74]                           - CACCTTTGCC TTTGCT                                                           - Oligo #53 R27IL3 Length: 000076                                             - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TATAACACAC NNSAAGCAGC                                                [SEQ ID NO:75]                           - CACCTTTGCC TTTGCT                                                           - Oligo #54 R28IL3 Length: 000076                                             - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TATAACACAC TTANNSCAGC                                                [SEQ ID NO:76]                           - CACCTTTGCC TTTGCT                                                           - Oligo #55 R29IL3 Length: 000094                                             - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TATAACACAC TTAAAGNNSC                                                [SEQ ID NO:77]                           - CACCTTTGCC TTTGCTGGAC TTCAACAACC TCAA                                       - Oligo #56 R30IL3 Length: 000094                                             - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TATAACACAC TTAAAGCAGN                                                [SEQ ID NO:78]                           - NSCCTTTGCC TTTGCTGGAC TTCAACAACC TCAA                                       - Oligo #57 R31IL3 Length: 000094                                             - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TATAACACAC TTAAAGCAGC                                                [SEQ ID NO:79]                           - CANNSTTGCC TTTGCTGGAC TTCAACAACC TCAA                                       - Oligo #58 R32IL3 Length: 000094                                             - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TATAACACAC TTAAAGCAGC                                                [SEQ ID NO:80]                           - CACCTNNSCC TTTGCTGGAC TTCAACAACC TCAA                                       - Oligo #59 R33IL3 Length: 000094                                             - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TATAACACAC TTAAAGCAGC                                                [SEQ ID NO:81]                           - CACCTTTGNN STTGCTGGAC TTCAACAACC TCAA                                       - Oligo #60 R34IL3 Length: 000094                                             - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TATAACACAC TTAAAGCAGC                                                [SEQ ID NO:82]                           - CACCTTTGCC TNNSCTGGAC TTCAACAACC TCAA                                       - Oligo #61 R35IL3 Length: 000065                                             - GCGCGCGATA TCTTGGTCTT CACCATTGAG GTTGTTGAAG TCSNNCAGCG GCAGCGGTGG                                                [SEQ ID NO:83]                           - CTGCT                                                                       - Oligo #62 R36IL3 Length: 000065                                             - GCGCGCGATA TCTTGGTCTT CACCATTGAG GTTGTTGAAS NNCAGCAGCG GCAGCG [SEQ                                               ID NO:84]                                - GTGGCTGCT                                                                   - Oligo #63 R37IL3 Length: 000065                                             - GCGCGCGATA TCTTGGTCTT CACCATTGAG GTTGTTSNNG TCCAGCAGCG GCAGCGGTGG                                                [SEQ ID NO:85]                           - CTGCT                                                                       - Oligo #64 R38IL3 Length: 000065                                             - GCGCGCGATA TCTTGGTCTT CACCATTGAG GTTSNNGAAG TCCAGCAGCG GCAGCGGTGG                                                [SEQ ID NO:86]                           - CTGCT                                                                       - Oligo #65 R39IL3 Length: 000065                                             - GCGCGCGATA TCTTGGTCTT CACCATTGAG SNNGTTGAAG TCCAGCAGCG GCAGCGGTGG                                                [SEQ ID NO:87]                           - CTGCT                                                                       - Oligo #66 R40IL3 Length: 000065                                             - GCGCGCGATA TCTTGGTCTT CACCATTSNN GTTGTTGAAG TCCAGCAGCG GCAGCGGTGG                                                [SEQ ID NO:88]                           - CTGCT                                                                       - Oligo #67 R41IL3 Length: 000083                                             - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT ATTTTCCATC AGGATATCTT GGTCTTCACC                                                [SEQ ID NO:89]                           - SNNGAGGTTG TTGAAGTCCA GCA                                                   - Oligo #68 R42IL3 Length: 000083                                             - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT ATTTTCCATC AGGATATCTT GGTCTTCSNN                                                [SEQ ID NO:90]                           - ATTGAGGTTG TTGAAGTCCA GCA                                                   - Oligo #69 R43IL3 Length: 000083                                             - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT ATTTTCCATC AGGATATCTT GGTCSNNACC                                                [SEQ ID NO:91]                           - ATTGAGGTTG TTGAAGTCCA GCA                                                   - Oligo #70 R44IL3 Length: 000083                                             - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT ATTTTCCATC AGGATATCTT GSNNTTCACC                                                [SEQ ID NO:92]                           - ATTGAGGTTG TTGAAGTCCA GCA                                                   - Oligo #71 R45IL3 Length: 000083                                             - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT ATTTTCCATC AGGATATCSN NGTCTTCACC                                                [SEQ ID NO:93]                           - ATTGAGGTTG TTGAAGTCCA GCA                                                   - Oligo #72 R46IL3 Length: 000083                                             - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT ATTTTCCATC AGGATSNNTT GGTCTTCACC                                                [SEQ ID NO:94]                           - ATTGAGGTTG TTGAAGTCCA GCA                                                   - Oligo #73 R47IL3 Length: 000065                                             - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT ATTTTCCATC AGSNNATCTT GGTCTTCACC                                                [SEQ ID NO:95]                           - ATTGA                                                                       - Oligo #74 R48IL3 Length: 000065                                             - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT ATTTTCCATS NNGATATCTT GGTCTTCACC                                                [SEQ ID NO:96]                           - ATTGA                                                                       - Oligo #75 R49IL3 Length: 000065                                             - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT ATTTTCSNNC AGGATATCTT GGTCTTCACC                                                [SEQ ID NO:97]                           - ATTGA                                                                       - Oligo #76 R50IL3 Length: 000065                                             - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT ATTSNNCATC AGGATATCTT GGTCTTCACC                                                [SEQ ID NO:98]                           - ATTGA                                                                       - Oligo #77 R51IL3 Length: 000065                                             - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT SNNTTCCATC AGGATATCTT GGTCTTCACC                                                [SEQ ID NO:99]                           - ATTGA                                                                       - Oligo #78 R52IL3 Length: 000065                                             - GCGCGCCTCG AGGTTTGGAC GACGAAGSNN ATTTTCCATC AGGATATCTT GGTCTTCACC                                                [SEQ ID NO:100]                          - ATTGA                                                                       - Oligo #79 R53IL3 Length: 000086                                             - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCACGGTTG AATGCCTCGA GGTTTGGACG                                                [SEQ ID NO:101]                          - ACGSNNGTTA TTTTCCATCA GGATAT                                                - Oligo #80 R54IL3 Length: 000086                                             - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCACGGTTG AATGCCTCGA GGTTTGGACG                                                [SEQ ID NO:102]                          - SNNAAGGTTA TTTTCCATCA GGATAT                                                - Oligo #81 R55IL3 Length: 000086                                             - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCACGGTTG AATGCCTCGA GGTTTGGSNN                                                [SEQ ID NO:103]                          - ACGAAGGTTA TTTTCCATCA GGATAT                                                - Oligo #82 R56IL3 Length: 000086                                             - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCACGGTTG AATGCCTCGA GGTTSNNACG                                                [SEQ ID NO:104]                          - ACGAAGGTTA TTTTCCATCA GGATAT                                                - Oligo #83 R57IL3 Length: 000086                                             - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCACGGTTG AATGCCTCGA GSNNTGGACG                                                [SEQ ID NO:105]                          - ACGAAGGTTA TTTTCCATCA GGATAT                                                - Oligo #84 R58IL3 Length: 000086                                             - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCACGGTTG AATGCCTCSN NGTTTGGACG                                                [SEQ ID NO:106]                          - ACGAAGGTTA TTTTCCATCA GGATAT                                                - Oligo #85 R59IL3 Length: 000068                                             - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCACGGTTG AATGCSNNGA GGTTTGGACG                                                [SEQ ID NO:107]                          - ACGAAGGT                                                                    - Oligo #86 R60IL3 Length: 000068                                             - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCACGGTTG AASNNCTCGA GGTTTGGACG                                                [SEQ ID NO:108]                          - ACGAAGGT                                                                    - Oligo #87 R61IL3 Length: 000068                                             - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCACGGTTS NNTGCCTCGA GGTTTGGACG                                                [SEQ ID NO:109]                          - ACGAAGGT                                                                    - Oligo #88 R62IL3 Length: 000068                                             - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCACGSNNG AATGCCTCGA GGTTTGGACG                                                [SEQ ID NO:110]                          - ACGAAGGT                                                                    - Oligo #89 R63IL3 Length: 000068                                             - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCSNNGTTG AATGCCTCGA GGTTTGGACG                                                [SEQ ID NO:111]                          - ACGAAGGT                                                                    - Oligo #90 R64IL3 Length: 000068                                             - GCGCGCTGAT GCATTCTGCA GAGACTTGAC SNNACGGTTG AATGCCTCGA GGTTTGGACG                                                [SEQ ID NO:112]                          - ACGAAGGT                                                                    - Oligo #91 R65IL3 Length: 000065                                             - GCGCGCCTCG AGGCATTCAA CCGTGCTNNS AAGTCTCTGC AGAATGCATC AGCAATTGAG                                                [SEQ ID NO:113]                          - AGCAT                                                                       - Oligo #92 R66IL3 Length: 000065                                             - GCGCGCCTCG AGGCATTCAA CCGTGCTGTC NNSTCTCTGC AGAATGCATC AGCAATTGAG                                                [SEQ ID NO:114]                          - AGCAT                                                                       - Oligo #93 R67IL3 Length: 000065                                             - GCGCGCCTCG AGGCATTCAA CCGTGCTGTC AAGNNSCTGC AGAATGCATC AGCAATTGAG                                                [SEQ ID NO:115]                          - AGCAT                                                                       - Oligo #94 R68IL3 Length: 000065                                             - GCGCGCCTCG AGGCATTCAA CCGTGCTGTC AAGTCTNNSC AGAATGCATC AGCAATTGAG                                                [SEQ ID NO:116]                          - AGCAT                                                                       - Oligo #95 R69IL3 Length: 000065                                             - GCGCGCCTCG AGGCATTCAA CCGTGCTGTC AAGTCTCTGN NSAATGCATC AGCAATTGAG                                                [SEQ ID NO:117]                          - AGCAT                                                                       - Oligo #96 R70IL3 Length: 000065                                             - GCGCGCCTCG AGGCATTCAA CCGTGCTGTC AAGTCTCTGC AGNNSGCATC AGCAATTGAG                                                [SEQ ID NO:118]                          - AGCAT                                                                       - Oligo #97 R71IL3 Length: 000053                                             - GCGCGCCTGC AGAATNNSTC AGCAATTGAG AGCATTCTTA AAAATCTCCT GCC [SEQ ID                                               NO:119]                                  - Oligo #98 R72IL3 Length: 000053                                             - GCGCGCCTGC AGAATGCANN SGCAATTGAG AGCATTCTTA AAAATCTCCT GCC [SEQ ID                                               NO:120]                                  - Oligo #99 R73IL3 Length: 000053                                             - GCGCGCCTGC AGAATGCATC ANNSATTGAG AGCATTCTTA AAAATCTCCT GCC [SEQ ID                                               NO:121]                                  - Oligo #100 R74IL3 Length: 000053                                            - GCGCGCCTGC AGAATGCATC AGCANNSGAG AGCATTCTTA AAAATCTCCT GCC [SEQ ID                                               NO:122]                                  - Oligo #101 R75IL3 Length: 000053                                            - GCGCGCCTGC AGAATGCATC AGCAATTNNS AGCATTCTTA AAAATCTCCT GCC [SEQ ID                                               NO:123]                                  - Oligo #102 R76IL3 Length: 000053                                            - GCGCGCCTGC AGAATGCATC AGCAATTGAG NNSATTCTTA AAAATCTCCT GCC [SEQ ID                                               NO:124]                                  - Oligo #103 R77IL3 Length: 000071                                            - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCNNSCTTA AAAATCTCCT GCCATGTCTG                                                [SEQ ID NO:125]                          - CCGCTAGCCA C                                                                - Oligo #104 R78IL3 Length: 000071                                            - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTNNSA AAAATCTCCT GCCATGTCTG                                                [SEQ ID NO:126]                          - CCGCTAGCCA C                                                                - Oligo #105 R79IL3 Length: 000071                                            - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTCTTN NSAATCTCCT GCCATGTCTG                                                [SEQ ID NO:127]                          - CCGCTAGCCA C                                                                - Oligo #106 R80IL3 Length: 000071                                            - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTCTTA AANNSCTCCT GCCATGTCTG                                                [SEQ ID NO:138]                          - CCGCTAGCCA C                                                                - Oligo #107 R81IL3 Length: 000071                                            - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTCTTA AAAATNNSCT GCCATGTCTG                                                [SEQ ID NO:139]                          - CCGCTAGCCA C                                                                - Oligo #108 R82IL3 Length: 000071                                            - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTCTTA AAAATCTCNN SCCATGTCTG                                                [SEQ ID NO:140]                          - CCGCTAGCCA C                                                                - Oligo #109 R83IL3 Length: 000089                                            - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTCTTA AAAATCTCCT GNNSTGTCTG                                                [SEQ ID NO:141]                          - CCGCTAGCCA CGGCCGCACC CACGCGACA                                             - Oligo #110 R84IL3 Length: 000089                                            - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTCTTA AAAATCTCCT GCCANNSCTG                                                [SEQ ID NO:142]                          - CCGCTAGCCA CGGCCGCACC CACGCGACA                                             - Oligo #111 R85IL3 Length: 000089                                            - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTCTTA AAAATCTCCT GCCATGTNNS                                                ]SEQ ID NO:143]                          - CCGCTAGCCA CGGCCGCACC CACGCGACA                                             - Oligo #112 R86IL3 Length: 000089                                            - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTCTTA AAAATCTCCT GCCATGTCTG                                                [SEQ ID NO:157]                          - NNSCTAGCCA CGGCCGCACC CACGCGACA                                             - Oligo #113 R87IL3 Length: 000089                                            - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTCTTA AAAATCTCCT GCCATGTCTG                                                [SEQ ID NO:158]                          - CCGNNSGCCA CGGCCGCACC CACGCGACA                                             - Oligo #114 R88IL3 Length: 000089                                            - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTCTTA AAAATCTCCT GCCATGTCTG                                                [SEQ ID NO:159]                          - CCGCTANNSA CGGCCGCACC CACGCGACA                                             - Oligo #115 R89IL3 Length: 000086                                            - CGCGCGGAAT TCATTCCAGT CACCGTCCTT GATATGGATT GGATGTCGCG TGGGTGCGGC                                                [SEQ ID NO:160]                          - SNNGGCCAGG GGCAGACATG GCAGGA                                                - Oligo #116 R90IL3 Length: 000086                                            - CGCGCGGAAT TCATTCCAGT CACCGTCCTT GATATGGATT GGATGTCGCG TGGGTGCSNN                                                [SEQ ID NO:161]                          - CGTGGCCAGG GGCAGACATG GCAGGA                                                - Oligo #117 R91IL3 Length: 000086                                            - CGCGCGGAAT TCATTCCAGT CACCGTCCTT GATATGGATT GGATGTCGCG TGGGSNNGGC                                                [SEQ ID NO:162]                          - CGTGGCCAGG GGCAGACATG GCAGGA                                                - Oligo #118 R92IL3 Length: 000086                                            - CGCGCGGAAT TCATTCCAGT CACCGTCCTT GATATGGATT GGATGTCGCG TSNNTGCGGC                                                [SEQ ID NO:163]                          - CGTGGCCAGG GGCAGACATG GCAGGA                                                - Oligo #119 R93IL3 Length: 000086                                            - CGCGCGGAAT TCATTCCAGT CACCGTCCTT GATATGGATT GGATGTCGSN NGGGTGCGGC                                                [SEQ ID NO:164]                          - CGTGGCCAGG GGCAGACATG GCAGGA                                                - Oligo #120 3PR106 Length: 000048                                            - TTTCAGATAG AAGGTCAGTT TACGACGGAA SNNATTCCAG TCACCGTC [SEQ ID NO:165]        - Oligo #121 3PR107 Length: 000048                                            - TTTCAGATAG AAGGTCAGTT TACGACGSNN TTCATTCCAG TCACCGTC [SEQ ID NO:166]        - Oligo #122 3PR108 Length: 000048                                            - TTTCAGATAG AAGGTCAGTT TACGSNNGAA TTCATTCCAG TCACCGTC [SEQ ID NO:167]        - Oligo #123 3PR109 Length: 000048                                            - TTTCAGATAG AAGGTCAGTT TSNNACGGAA TTCATTCCAG TCACCGTC [SEQ ID NO:168]        - Oligo #124 3PR110 Length: 000048                                            - TTTCAGATAG AAGGTCAGSN NACGACGGAA TTCATTCCAG TCACCGTC [SEQ ID NO:169]        - Oligo #125 3PR111 Length: 000048                                            - TTTCAGATAG AAGGTSNNTT TACGACGGAA TTCATTCCAG TCACCGTC [SEQ ID NO:170]        - Oligo #126 IL3MUTD3 Length: 000023                                          - CGCGCGAAGC TTATTACTGT TGA [SEQ ID NO:171]                                   - Oligo #127 R112IL3 Length: 000078                                           - CGCGCGAAGC TTATTACTGT TGAGCCTGCG CGTTCTCCAA GGTTTTCAGA TAGAASNNCA                                                [SEQ ID NO:172]                          - GTTTACGACG GAATTCAT                                                         - Oligo #128 R113IL3 Length: 000078                                           - CGCGCGAAGC TTATTACTGT TGAGCCTGCG CGTTCTCCAA GGTTTTCAGA TASNNGGTCA                                                [SEQ ID NO:173]                          - GTTTACGACG GAATTCAT                                                         - Oligo #129 R114IL3 Length: 000078                                           - CGCGCGAAGC TTATTACTGT TGAGCCTGCG CGTTCTCCAA GGTTTTCAGS NNGAAGGTCA                                                [SEQ ID NO:174]                          - GTTTACGACG GAATTCAT                                                         - Oligo #130 R115IL3 Length: 000078                                           - CGCGCGAAGC TTATTACTGT TGAGCCTGCG CGTTCTCCAA GGTTTTCAGS NNGAAGGTCA                                                [SEQ ID NO:175]                          - GTTTACGACG GAATTCAT                                                         - Oligo #131 R116IL3 Length: 000078                                           - CGCGCGAAGC TTATTACTGT TGAGCCTGCG CGTTCTCCAA GGTSNNCAGA TAGAAGGTCA                                                [SEQ ID NO:176]                          - GTTTACGACG GAATTCAT                                                         - Oligo #132 R117IL3 Length: 000078                                           - CGCGCGAAGC TTATTACTGT TGAGCCTGCG CGTTCTCCAA SNNTTTCAGA TAGAAGGTCA                                                [SEQ ID NO:177]                          - GTTTACGACG GAATTCAT                                                         - Oligo #133 R118IL3 Length: 000060                                           - CGCGCGAAGC TTATTACTGT TGAGCCTGCG CGTTCTCSNN GGTTTTCAGA TAGAAGGTCA                                                [SEQ ID NO:178]                          - Oligo #134 R119IL3 Length: 000060                                           - CGCGCGAAGC TTATTACTGT TGAGCCTGCG CGTTSNNCAA GGTTTTCAGA TAGAAGGTCA                                                [SEQ ID NO:179]                          - Oligo #135 R120IL3 Length: 000060                                           - CGCGCGAAGC TTATTACTGT TGAGCCTGCG CSNNCTCCAA GGTTTTCAGA TAGAAGGTCA                                                [SEQ ID NO:180]                          - Oligo #136 R121IL3 Length: 000060                                           - CGCGCGAAGC TTATTACTGT TGAGCCTGSN NGTTCTCCAA GGTTTTCAGA TAGAAGGTCA                                                [SEQ ID NO:181]                          - Oligo #137 R122IL3 Length: 000060                                           - CGCGCGAAGC TTATTACTGT TGAGCSNNCG CGTTCTCCAA GGTTTTCAGA TAGAAGGTCA                                                [SEQ ID NO:182]                          - Oligo #138 R123IL3 Length: 000060                                           - CGCGCGAAGC TTATTACTGT TGSNNCTGCG CGTTCTCCAA GGTTTTCAGA TAGAAGGTCA                                                [SEQ ID NO:183]                          - Oligo #139 P1722IL3 Length: 000024                                          - TGCTCTAACA TGATCGATGA AATT [SEQ ID NO:184]                                  - Oligo #140 P2328IL3 Length: 000024                                          - GAAATTATAA CACACTTAAA GCAG [SEQ ID NO:185]                                  - Oligo #141 P2934IL3 Length: 000024                                          - AAGCAGCCAC CTTTGCCTTT GCTG [SEQ ID NO:186]                                  - Oligo #142 P3540IL3 Length: 000024                                          - AAGCAGCCAC CGCTGCCGCT GCTG [SEQ ID NO:187]                                  - Oligo #143 PRB41-46 Length: 000024                                          - CTCAATGGTG AAGACCAAGA TATC [SEQ ID NO:188]                                  - Oligo #144 PRB47-52 Length: 000024                                          - GATATCCTGA TGGAAAATAA CCTT [SEQ ID NO:189]                                  - Oligo #145 PRB53-58 Length: 000024                                          - AACCTTCGTC GTCCAAACCT CGAG [SEQ ID NO:190]                                  - Oligo #146 PRB59-64 Length: 000024                                          - CTCGAGGCAT TCAACCGTGC TGTC [SEQ ID NO:191]                                  - Oligo #147 PRB65-70 Length: 000024                                          - GCTGTCAAGT CTCTGCAGAA TGCA [SEQ ID NO:192]                                  - Oligo #148 P7176IL3 Length: 000024                                          - AATGCATCAG CAATTGAGAG CATT [SEQ ID NO:193]                                  - Oligo #149 P7782IL3 Length: 000024                                          - AGCATTCTTA AAAATCTCCT GCCA [SEQ ID NO:194]                                  - Oligo #150 P8388IL3 Length: 000024                                          - CTGCCATGTC TGCCCCTGGC CACG [SEQ ID NO:195]                                  - Oligo #151 P8893IL3 Length: 000024                                          - CTGGCCACGG CCGCACCCAC GCGA [SEQ ID NO:196]                                  - Oligo #152 P106111 Length: 000024                                           - AATGAATTCC GTCGTAAACT GACC [SEQ ID NO:197]                                  - Oligo #153 P112117 Length: 000024                                           - CTGACCTTCT ATCTGAAAAC CTTG [SEQ ID NO:198]                                  - Oligo #154 P118123 Length: 000024                                           - ACCTTGGAGA ACGCGCAGGC TCAA [SEQ ID NO:199]                                  - Oligo #155 PSTERCI1.REQ Length: 000022                                      - GAATGCATCA GCAATTGAGA GC [SEQ ID NO:200]                                    - Oligo #156 PSTECRI5.REQ Length: 000020                                      - AATTGCTGAT GCATTCTGCA [SEQ ID NO:201]                                       - Oligo #157 PSTECRI2.REQ Length: 000024                                      - ATTCTTAAAA ATCTCCTGCC ATGT [SEQ ID NO:202]                                  - Oligo #158 PSTECRI6.REQ Length: 000024                                      - CAGGAGATTT TTAAGAATGC TCTC [SEQ ID NO:203]                                  - Oligo #159 PSTECRI3.REQ Length: 000030                                      - CTGCCCCTGG CCACGGCCGC ACCCACGCGA [SEQ ID NO:204]                            - Oligo #160 PSTECRI7.REQ Length: 000030                                      - GGGTGCGGCC GTGGCCAGGG GCAGACATGG [SEQ ID NO:205]                            - Oligo #161 98I100R4.REQ Length: 000034                                      - CATCCAATCA TCATCCGTGA CGGTGACTGG AATG [SEQ ID NO:206]                       - Oligo #162 98I100R8.REQ Length: 000044                                      - AATTCATTCC AGTCACCGTC ACGGATGATG ATTGGATGTC GCGT [SEQ ID NO:207]                                                   - Oligo #163 95R8I0R4.REQ                                                   Length: 000034                           - CGCCCAATCA TCATCCGTGA CGGTGACTGG AATG [SEQ ID NO:208]                       - Oligo #164 95R8I0R8.REQ Length: 000044                                      - AATTCATTCC AGTCACCGTC ACGGATGATG ATTGGGCGTC GCGT [SEQ ID NO:209]                                                   - Oligo #165 NCOECRV1.REQ                                                   Length: 000040                           - CATGGCTAAC TGCTCTAACA TGATCGATGA AATTATAACA [SEQ ID NO:210]                 - Oligo #166 NCOECRV4.REQ Length: 000045                                      - CTTTAAGTGT GTTATAATTT CATCGATCAT GTTAGAGCAG TTAGC [SEQ ID NO:211]                                                  - Oligo #167 NCOECRV2.REQ                                                   Length: 000036                           - CACTTAAAGC AGCCACCTTT GCCTTTGCTG GACTTC [SEQ ID NO:212]                     - Oligo #168 NCOECRV5.REQ Length: 000036                                      - GAGGTTGTTG AAGTCCAGCA AAGGCAAAGG TGGCTG [SEQ ID NO:213]                     - Oligo #169 2D5M6SUP.REQ Length: 000027                                      - AACAACCTCA ATGACGAAGA CATGTCT [SEQ ID NO:214]                               - Oligo #170 2D5M6SLO.REQ Length: 000018                                      - AGACATGTCT TCGTCATT [SEQ ID NO:215]                                         - Oligo #15(A) Length: 000016                                                 - TGAACCATAT GTCAGG [SEQ ID NO:29]                                            - Oligo #16(A) Length: 000024                                                 - AATTCCTGAC ATATGGTTCA TGCA [SEQ ID NO:30]                                   - Oligo #51(A) Length: 000034                                                 - GCCGATACCGCGGCATACTCCCACCATTCAGAGA [SEQ ID NO:155]                          - Oligo #52(A) Length: 000033                                                 - GCCGATAAGATCTAAAACGGGTATGGAGAAACA [SEQ ID NO:156]                           - Oligo #171 Length: 000040                                                   - CATGGCTAAC TGCTCTAACA TGATCAACGA AATTATAACA [SEQ ID NO:69]                  - Oligo #172 Length: 000045                                                   - CTTTAAGTGT GTTATAATTT CGTTGATCAT GTTAGAGCAG TTAGC [SEQ ID NO:70]                                                   - Oligo #173 Length: 000040                                                   - CATGGCTAAC TGCTCTAACA                                                     TGATCCAAGA AATTATAACA [SEQ ID                                                 NO:71]                                   - Oligo #174 Length: 000045                                                   - CTTTAAGTGT GTTATAATTT CTTGGATCAT GTTAGAGCAG TTAGC [SEQ ID NO:72]                                                   - Oligo #175 Length: 000040                                                   - CATGGCTAAC TGCTCTAACA                                                     TGATCGAAGA AATTATAACA [SEQ ID                                                 NO:73]                                   - Oligo #176 Length: 000045                                                   - CTTTAAGTGT GTTATAATTT CTTCGATCAT GTTAGAGCAG TTAGC [SEQ ID NO:219]                                                  - Oligo #177 Length: 000040                                                   - CATGGCTAAC TGCTCTAACA                                                     TGATCAGCGA AATTATAACA [SEQ ID                                                 NO:230]                                  - Oligo #178 Length: 000045                                                   - CTTTAAGTGT GTTATAATTT CGCTGATCAT GTTAGAGCAG TTAGC [SEQ ID NO:231]                                                  - Oligo #179 Length: 000040                                                   - CATGGCTAAC TGCTCTAACA                                                     TGATCACCGA AATTATAACA [SEQ ID                                                 NO:232]                                  - Oligo #180 Length: 000045                                                   - CTTTAAGTGT GTTATAATTT CCGTGATCAT GTTAGAGCAG TTAGC [SEQ ID NO:233]                                                  - Oligo #181 Length: 000040                                                   - CATGGCTAAC TGCTCTAACA                                                     TGATCGATAA CATTATAACA [SEQ ID                                                 NO:234]                                  - Oligo #182 Length: 000045                                                   - CTTTAAGTGT GTTATAATGT TATCGATCAT GTTAGAGCAG TTAGC [SEQ ID NO:235]                                                  - Oligo #183 Length: 000040                                                   - CATGGCTAAC TGCTCTAACA                                                     TGATCGATGA CATTATAACA [SEQ ID                                                 NO:236]                                  - Oligo #184 Length: 000045                                                   - CTTTAAGTGT GTTATAATGT CATCGATCAT GTTAGAGCAG TTAGC [SEQ ID NO:237]                                                  - Oligo #185 Length: 000040                                                   - CATGGCTAAC TGCTCTAACA                                                     TGATCGATCA GATTATAACA [SEQ ID                                                 NO:238]                                  - Oligo #186 Length: 000045                                                   - CTTTAAGTGT GTTATAATCT GATCGATCAT GTTAGAGCAG TTAGC [SEQ ID NO:239]                                                  - Oligo #187 Length: 000040                                                   - CATGGCTAAC TGCTCTAACA                                                     TGATCGATCT GATTATAACA [SEQ ID                                                 NO:240]                                  - Oligo #188 Length: 000045                                                   - CTTTAAGTGT GTTATAATCA GATCGATCAT GTTAGAGCAG TTAGC [SEQ ID NO:241]                                                  - Oligo #189 Length: 000040                                                   - CATGGCTAAC TGCTCTAACA                                                     TGATCGATGT TATTATAACA [SEQ ID                                                 NO:242]                                  - Oligo #190 Length: 000045                                                   - CTTTAAGTGT GTTATAATAA CATCGATCAT GTTAGAGCAG TTAGC [SEQ ID NO:243]                                                  - Oligo #191 Length: 000036                                                   - CACTTAAAGC AGCCACCTTT                                                     GCCTGCTCTG GACTTC [SEQ ID NO:244]        - Oligo #192 Length: 000036                                                   - GAGGTTGTTG AAGTCCAGAG CAGGCAAAGG TGGCTG [SEQ ID NO:245]                     - Oligo #193 Length: 000036                                                   - CACTTAAAGC AGCCACCTTT GCCTCGTCTG GACTTC [SEQ ID NO:246]                     - Oligo #194 Length: 000036                                                   - GAGGTTGTTG AAGTCCAGAC GAGGCAAAGG TGGCTG [SEQ ID NO:247]                     - Oligo #195 Length: 000036                                                   - CACTTAAAGC AGCCACCTTT GCCTCAGCTG GACTTC [SEQ ID NO:248]                     - Oligo #196 Length: 000036                                                   - GAGGTTGTTG AAGTCCAGCT GAGGCAAAGG TGGCTG [SEQ ID NO:249]                     - Oligo #197 Length: 000036                                                   - CACTTAAAGC AGCCACCTTT GCCTGAACTG GACTTC [SEQ ID NO:250]                     - Oligo #198 Length: 000036                                                   - GAGGTTGTTG AAGTCCAGCT CAGGCAAAGG TGGCTG [SEQ ID NO:251]                     - Oligo #199 Length: 000036                                                   - CACTTAAAGC AGCCACCTTT GCCTATCCTG GACTTC [SEQ ID NO:252]                     - Oligo #200 Length: 000036                                                   - GAGGTTGTTG AAGTCCAGGA TAGGCAAAGG TGGCTG [SEQ ID NO:253]                     - Oligo #201 Length: 000036                                                   - CACTTAAAGC AGCCACCTTT CCCTTTCCTG GACTTC [SEQ ID NO:254]                     - Oligo #202 Length: 000036                                                   - GAGGTTGTTG AAGTCCAGGA AAGGCAAAGG TGGCTG [SEQ ID NO:255]                     - Oligo #203 Length: 000036                                                   - CACTTAAAGC AGCCACCTTT GCCTACCCTG GACTTC [SEQ ID NO:256]                     - Oligo #204 Length: 000036                                                   - GAGGTTGTTG AAGTCCAGGG TAGGCAAAGG TGGCTG [SEQ ID NO:257]                     - Oligo #205 Length: 000027                                                   - AACAACCTCA ATCGTGAAGA CCAAGAT [SEQ ID NO:258]                               - Oligo #206 Length: 000018                                                   - ATCTTGGTCT TCACGATT [SEQ ID NO:259]                                         - Oligo #207 Length: 000027                                                   - AACAACCTCA ATAACGAAGA CCAAGAT [SEQ ID NO:260]                               - Oligo #208 Length: 000018                                                   - ATCTTGGTCT TCGTTATT [SEQ ID NO:261]                                         - Oligo #209 Length: 000027                                                   - AACAACCTCA ATGAAGAAGA CCAAGAT [SEQ ID NO:262]                               - Oligo #210 Length: 000018                                                   - ATCTTGGTCT TCTTCATT [SEQ ID NO:263]                                         - Oligo #211 Length: 000027                                                   - AACAACCTCA ATATCGAAGA CCAAGAT [SEQ ID NO:264]                               - Oligo #212 Length: 000018                                                   - ATCTTGGTCT TCGATATT [SEQ ID NO:265]                                         - Oligo #213 Length: 000027                                                   - AACAACCTCA ATCTGGAAGA CCAAGAT [SEQ ID NO:266]                               - Oligo #214 Length: 000018                                                   - ATCTTGGTCT TCCAGATT [SEQ ID NO:267]                                         - Oligo #215 Length: 000027                                                   - AACAACCTCA ATAAAGAAGA CCAAGAT [SEQ ID NO:268]                               - Oligo #216 Length: 000018                                                   - ATCTTGGTCT TCTTTATT [SEQ ID NO:269]                                         - Oligo #217 Length: 000027                                                   - AACAACCTCA ATATGGAAGA CCAAGAT [SEQ ID NO:270]                               - Oligo #218 Length: 000018                                                   - ATCTTGGTCT TCCATATT [SEQ ID NO:271]                                         - Oligo #219 Length: 000027                                                   - AACAACCTCA ATTTCGAAGA CCAAGAT [SEQ ID NO:272]                               - Oligo #220 Length: 000018                                                   - ATCTTGGTCT TCGAAATT [SEQ ID NO:273]                                         - Oligo #221 Length: 000027                                                   - AACAACCTCA ATACCGAAGA CCAAGAT [SEQ ID NO:274]                               - Oligo #222 Length: 000018                                                   - ATCTTGGTCT TCGGTATT [SEQ ID NO:275]                                         - Oligo #223 Length: 000027                                                   - AACAACCTCA ATTACGAAGA CCAAGAT [SEQ ID NO:276]                               - Oligo #224 Length: 000018                                                   - ATCTTGGTCT TCGTAATT [SEQ ID NO:277]                                         - Oligo #225 Length: 000027                                                   - AACAACCTCA ATGTTGAAGA CCAAGAT [SEQ ID NO:278]                               - Oligo #226 Length: 000018                                                   - ATCTTGGTCT TCAACATT [SEQ ID NO:279]                                         - Oligo #227 Length: 000027                                                   - AACAACCTCA ATGGGCGTGA CCAAGAT [SEQ ID NO:280]                               - Oligo #228 Length: 000018                                                   - ATCTTGGTCT CGCCCATT [SEQ ID NO:281]                                         - Oligo #229 Length: 000027                                                   - AACAACCTCA ATGGGCAGGA CCAAGAT [SEQ ID NO:282]                               - Oligo #230 Length: 000018                                                   - ATCTTGGTCC TGCCCATT [SEQ ID NO:283]                                         - Oligo #231 Length: 000027                                                   - AACAACCTCA ATGGGGGTGA CCAAGAT [SEQ ID NO:284]                               - Oligo #232 Length: 000018                                                   - ATCTTGGTCA CCCCCATT [SEQ ID NO:285]                                         - Oligo #233 Length: 000027                                                   - AACAACCTCA ATGGGACCGA CCAAGAT [SEQ ID NO:286]                               - Oligo #234 Length: 000018                                                   - ATCTTGGTCG GTCCCATT [SEQ ID NO:287]                                         - Oligo #235 Length: 000027                                                   - AACAACCTCA ATGGGGAAGC TCAAGAT [SEQ ID NO:288]                               - Oligo #236 Length: 000018                                                   - ATCTTGAGCT TCCCCATT [SEQ ID NO:289]                                         - Oligo #237 Length: 000027                                                   - AACAACCTCA ATGGGGAAAA CCAAGAT [SEQ ID NO:290]                               - Oligo #238 Length: 000018                                                   - ATCTTGGTTT TCCCCATT [SEQ ID NO:291]                                         - Oligo #239 Length: 000027                                                   - AACAACCTCA ATGGGGAACA GCAAGAT [SEQ ID NO:292]                               - Oligo #240 Length: 000018                                                   - ATCTTGCTGT TCCCCATT [SEQ ID NO:293]                                         - Oligo #241 Length: 000027                                                   - AACAACCTCA ATGGGGAAGA ACAAGAT [SEQ ID NO:294]                               - Oligo #242 Length: 000018                                                   - ATCTTGTTCT TCCCCATT [SEQ ID NO:295]                                         - Oligo #243 Length: 000027                                                   - AACAACCTCA ATGGGGAAGA CGCTGAT [SEQ ID NO:296]                               - Oligo #244 Length: 000018                                                   - ATCAGCGTCT TCCCCATT [SEQ ID NO:297]                                         - Oligo #245 Length: 000027                                                   - AACAACCTCA ATGGGGAAGA CCGTGAT [SEQ ID NO:298]                               - Oligo #246 Length: 000018                                                   - ATCACGGTCT TCCCCATT [SEQ ID NO:299]                                         - Oligo #247 Length: 000027                                                   - AACAACCTCA ATGGGGAAGA CAACGAT [SEQ ID NO:300]                               - Oligo #248 Length: 000018                                                   - ATCGTTGTCT TCCCCATT [SEQ ID NO:301]                                         - Oligo #249 Length: 000027                                                   - AACAACCTCA ATGGGGAAGA CGACGAT [SEQ ID NO:302]                               - Oligo #250 Length: 000018                                                   - ATCGTCGTCT TCCCCATT [SEQ ID NO:303]                                         - Oligo #251 Length: 000027                                                   - AACAACCTCA ATGGTGAAGA CGAAGAT [SEQ ID NO:304]                               - Oligo #252 Length: 000018                                                   - ATCTTCGTCT TCCCCATT [SEQ ID NO:305]                                         - Oligo #253 Length: 000027                                                   - AACAACCTCA ATGGTGAAGA CCACGAT [SEQ ID NO:306]                               - Oligo #254 Length: 000018                                                   - ATCGTGGTCT TCCCCATT [SEQ ID NO:307]                                         - Oligo #255 Length: 000027                                                   - AACAACCTCA ATGGGGAAGA CATCGAT [SEQ ID NO:308]                               - Oligo #256 Length: 000018                                                   - ATCGATGTCT TCCCCATT [SEQ ID NO:309]                                         - Oligo #257 Length: 000027                                                   - AACAACCTCA ATGGGGAAGA CTCCGAT [SEQ ID NO:310]                               - Oligo #258 Length: 000018                                                   - ATCGGAGTCT TCCCCATT [SEQ ID NO:311]                                         - Oligo #259 Length: 000027                                                   - AACAACCTCA ATGGGGAAGA CCAAGCT [SEQ ID NO:312]                               - Oligo #260 Length: 000018                                                   - AGCTTGGTCT TCCCCATT [SEQ ID NO:313]                                         - Oligo #261 Length: 000027                                                   - AACAACCTCA ATGGGGAAGA CCAAAAC [SEQ ID NO:314]                               - Oligo #262 Length: 000018                                                   - GTTTTGGTCT TCCCCATT [SEQ ID NO:315]                                         - Oligo #263 Length: 000027                                                   - AACAACCTCA ATGGGGAAGA CCAACAG [SEQ ID NO:316]                               - Oligo #264 Length: 000018                                                   - CTGTTGGTCT TCCCCATT [SEQ ID NO:317]                                         - Oligo #265 Length: 000027                                                   - AACAACCTCA ATGGGGAAGA CCAAGAA [SEQ ID NO:318]                               - Oligo #266 Length: 000018                                                   - TTCTTGGTCT TCCCCATT [SEQ ID NO:319]                                         - Oligo #267 Length: 000027                                                   - AACAACCTCA ATGGGGAAGA CCAACAC [SEQ ID NO:320]                               - Oligo #268 Length: 000018                                                   - GTGTTGGTCT TCCCCATT [SEQ ID NO:321]                                         - Oligo #269 Length: 000027                                                   - AACAACCTCA ATGGGGAAGA CCAAATC [SEQ ID NO:322]                               - Oligo #270 Length: 000018                                                   - GATTTGGTCT TCCCCATT [SEQ ID NO:323]                                         - Oligo #271 Length: 000027                                                   - AACAACCTCA ATGGGGAAGA CCAACTG [SEQ ID NO:324]                               - Oligo #272 Length: 000018                                                   - CAGTTGGTCT TCCCCATT [SEQ ID NO:325]                                         - Oligo #273 Length: 000027                                                   - AACAACCTCA ATGGGGAAGA CCAAAAA [SEQ ID NO:326]                               - Oligo #274 Length: 000018                                                   - TTTTTGGTCT TCCCCATT [SEQ ID NO:327]                                         - Oligo #275 Length: 000027                                                   - AACAACCTCA ATGGGGAAGA CCAATAC [SEQ ID NO:328]                               - Oligo #276 Length: 000018                                                   - GTATTGGTCT TCCCCATT [SEQ ID NO:329]                                         - Oligo #277 Length: 000027                                                   - AACAACCTCA ATGGGGAAGA CCAAGTT [SEQ ID NO:330]                               - Oligo #278 Length: 000018                                                   - AACTTGGTCT TCCCCATT [SEQ ID NO:331]                                         - Oligo #279 Length: 000036                                                   - ATCGCTATGG AAAATAACCT TCGAAGGCCA AACCTG [SEQ ID NO:332]                     - Oligo #280 Length: 000027                                                   - CCTTCGAAGG TTATTTTCCA TAGCGAT [SEQ ID NO:333]                               - Oligo #281 Length: 000036                                                   - ATCGAAATGG AAAATAACCT TCGAAGGCCA AACCTG [SEQ ID NO:334]                     - Oligo #282 Length: 000027                                                   - CCTTCGAAGG TTATTTTCCA TTTCGAT [SEQ ID NO:335]                               - Oligo #283 Length: 000036                                                   - ATCAAAATGG AAAATAACT TCGAAGGCCA AACCTG [SEQ ID NO:336]                      - Oligo #284 Length: 000027                                                   - CCTTCGAAGG TTATTTTCCA TTTTGAT [SEQ ID NO:337]                               - Oligo #285 Length: 000036                                                   - ATCATGATGG AAAATAACCT TCGAAGGCCA AACCTG [SEQ ID NO:338]                     - Oligo #286 Length: 000027                                                   - CCTTCGAAGG TTATTTTCA TCATGAT [SEQ ID NO:339]                                - Oligo #287 Length: 000036                                                   - ATCACCATGG AAAATAACCT TCGAAGGCCA AACCTG [SEQ ID NO:340]                     - Oligo #288 Length: 000027                                                   - CCTTCGAAGG TTATTTTCCA TGGTGAT [SEQ ID NO:341]                               - Oligo #289 Length: 000036                                                   - ATCGTTATGG AAAATAACCT TCGAAGGCCA AACCTG [SEQ ID NO:342]                     - Oligo #290 Length: 000027                                                   - CCTTCGAAGG TTATTTTCCA TAACGAT [SEQ ID NO:343]                               - Oligo #291 Length: 000036                                                   - ATCCTGATGC ACAATAACCT TCGAAGGCCA AACCTG [SEQ ID NO:344]                     - Oligo #292 Length: 000027                                                   - CCTTCGAAGG TTATTGTGCA TCAGGAT [SEQ ID NO:345]                               - Oligo #293 Length: 000036                                                   - ATCCTGATGA TGAATAACCT TCGAAGGCCA AACCTG [SEQ ID NO:346]                     - Oligo #294 Length: 000027                                                   - CCTTCGAAGG TTATTCATCA TCAGGAT [SEQ ID NO:347]                               - Oligo #295 Length: 000036                                                   - ATCCTGATGT TCAATAACCT TCGAAGGCA AACCTG [SEQ ID NO:348]                      - Oligo #296 Length: 000027                                                   - CCTTCGAAGG TTATTGAACA TCAGGAT [SEQ ID NO:349]                               - Oligo #297 Length: 000036                                                   - ATCCTGATGG CTAATAACCT TCGAAGGCCA AACCTG [SEQ ID NO:350]                     - Oligo #298 Length: 000027                                                   - CCTTCGAAGG TTATTAGCCA TCAGGAT [SEQ ID NO:351]                               - Oligo #299 Length: 000036                                                   - ATCCTGATGA ACAATAACCT TCGAAGGCCA AACCTG [SEQ ID NO:352]                     - Oligo #300 Length: 000027                                                   - CCTTCGAAGG TTATTGTTCA TCAGGAT [SEQ ID NO:353]                               - Oligo #301 Length: 000036                                                   - ATCCTGATGA TCAATAACCT TCGAAGGCCA AACCTG [SEQ ID NO:354]                     - Oligo #302 Length: 000027                                                   - CCTTCGAAGG TTATTGATCA TCAGGAT [SEQ ID NO:355]                               - Oligo #303 Length: 000036                                                   - ATCCTGATGA AAAATAACCT TCGAAGGCCA AACCTG [SEQ ID NO:356]                     - Oligo #304 Length: 000027                                                   - CCTTCGAAGG TTATTTTTCA TCAGGAT [SEQ ID NO:357]                               - Oligo #305 Length: 000036                                                   - ATCCTGATGT CCAATAACCT TCGAAGGCCA AACCTG [SEQ ID NO:358]                     - Oligo #306 Length: 000027                                                   - CCTTCGAAGG TTATTGGACA TCAGGAT [SEQ ID NO:359]                               - Oligo #307 Length: 000036                                                   - ATCCTGATGG TTAATAACCT TCGAAGGCCA AACCTG [SEQ ID NO:360]                     - Oligo #308 Length: 000027                                                   - CCTTCGAAGG TTATTAACCA TCAGGAT [SEQ ID NO:361]                               - Oligo #309 Length: 000036                                                   - ATCCTGATGG AAAATAACCT TGCTAGGCCA AACCTG [SEQ ID NO:362]                     - Oligo #310 Length: 000027                                                   - CCTAGCAAGG TTATTTTCCA TCAGGAT [SEQ ID NO:363]                               - Oligo #311 Length: 000036                                                   - ATCCTGATGG AAAATAACCT TAACAGGCCA AACCTG [SEQ ID NO:364]                     - Oligo #312 Length: 000027                                                   - CCTGTTAAGG TTATTTTCCA TCAGGAT [SEQ ID NO:365]                               - Oligo #313 Length: 000036                                                   - ATCCTGATGG AAAATAACCT TCACAGGCCA AACCTG [SEQ ID NO:366]                     - Oligo #314 Length: 000027                                                   - CCTGTGAAGG TTATTTTCCA TCAGGAT [SEQ ID NO:367]                               - Oligo #315 Length: 000036                                                   - ATCCTGATGG AAAATAACCT TAAAAGGCCA AACCTG [SEQ ID NO:368]                     - Oligo #316 Length: 000027                                                   - CCTTTTAAGG TTATTTTCCA TCAGGAT [SEQ ID NO:369]                               - Oligo #317 Length: 000036                                                   - ATCCTGATGG AAAATAACCT TCGAAGGGCT AACCTG [SEQ ID NO:370]                     - Oligo #318 Length: 000024                                                   - CCTGTTGAAT GCCTCCAGGT TAGC [SEQ ID NO:371]                                  - Oligo #319 Length: 000036                                                   - ATCCTGATGG AAAATAACCT TCGAAGGCGT AACCTG [SEQ ID NO:372]                     - Oligo #320 Length: 000024                                                   - CCTGTTGAAT GCCTCCAGGT TACG [SEQ ID NO:373]                                  - Oligo #321 Length: 000036                                                   - ATCCTGATGG AAAATAACCT TCGAAGGAAC AACCTG [SEQ ID NO:374]                     - Oligo #322 Length: 000024                                                   - CCTGTTGAAT GCCTCCAGGT TGTT [SEQ ID NO:375]                                  - Oligo #323 Length: 000036                                                   - ATCCTGATGG AAAATAACCT TCGAAGGGAA AACCTG [SEQ ID NO:376]                     - Oligo #324 Length: 000024                                                   - CCTGTTGAAT GCCTCCAGGT TTTC [SEQ ID NO:377]                                  - Oligo #325 Length: 000036                                                   - ATCCTGATGG AAAATAACCT TCGAAGGCAC AACCTG [SEQ ID NO:378]                     - Oligo #326 Length: 000024                                                   - CCTGTTGAAT GCCTCCAGGT TGTG [SEQ ID NO:379]                                  - Oligo #327 Length: 000036                                                   - ATCCTGATGG AAAATAACCT TCGAAGGCTG AACCTG [SEQ ID NO:380]                     - Oligo #328 Length: 000024                                                   - CCTGTTGAAT GCCTCCAGGT TCAG [SEQ ID NO:381]                                  - Oligo #329 Length: 000036                                                   - ATCCTGATGG AAAATAACCT TCGAAGGTTC AACCTG [SEQ ID NO:382]                     - Oligo #330 Length: 000024                                                   - CCTGTTGAAT GCCTCCAGGT TGAA [SEQ ID NO:383]                                  - Oligo #331 Length: 000036                                                   - ATCCTGATGG AAAATAACCT TCGAAGGACC AACCTG [SEQ ID NO:384]                     - Oligo #332 Length: 000024                                                   - CCTGTTGAAT GCCTCCAGGT TGGT [SEQ ID NO:385]                                  - Oligo #333 Length: 000036                                                   - ATCCTGATGG AAAATAACCT TCGAAGGTAC AACCTG [SEQ ID NO:386]                     - Oligo #334 Length: 000024                                                   - CCTGTTGAAT GCCTCCAGGT TGTA [SEQ ID NO:387]                                  - Oligo #335 Length: 000036                                                   - ATCCTGATGG AAAATAACT TCGAAGGGTT AACCTG [SEQ ID NO:388]                      - Oligo #336 Length: 000024                                                   - CCTGTTGAAT GCCTCCAGGT TAAC [SEQ ID NO:389]                                  - Oligo #337 Length: 000018                                                   - AAAAATCTCG CTCCATGT [SEQ ID NO:390]                                         - Oligo #338 Length: 000018                                                   - AGCGAGATTT TTAAGAAT [SEQ ID NO:391]                                         - Oligo #339 Length: 000018                                                   - AAAAATCTCA ACCCATGT [SEQ ID NO:392]                                         - Oligo #340 Length: 000018                                                   - GTTGAGATTT TTAAGAAT [SEQ ID NO:393]                                         - Oligo #341 Length: 000018                                                   - AAAAATCTCG AACCATGT [SEQ ID NO:394]                                         - Oligo #342 Length: 000018                                                   - TTCGAGATTT TTAAGAAT [SEQ ID NO:395]                                         - Oligo #343 Length: 000018                                                   - AAAAATCTCC ACCCATGT [SEQ ID NO:396]                                         - Oligo #344 Length: 000018                                                   - GTGGAGATTT TTAAGAAT [SEQ ID NO:397]                                         - Oligo #345 Length: 000018                                                   - AAAAATCTCA TCCCATGT [SEQ ID NO:398]                                         - Oligo #346 Length: 000018                                                   - GATGAGATTT TTAAGAAT [SEQ ID NO:399]                                         - Oligo #347 Length: 000018                                                   - AAAAATCTCA TGCCATGT [SEQ ID NO:400]                                         - Oligo #348 Length: 000018                                                   - CATGAGATTT TTAAGAAT [SEQ ID NO:401]                                         - Oligo #349 Length: 000018                                                   - AAAAATCTCT TCCCATGT [SEQ ID NO:402]                                         - Oligo #350 Length: 000018                                                   - GAAGAGATTT TTAAGAAT [SEQ ID NO:403]                                         - Oligo #351 Length: 000018                                                   - AAAAATCTCT CCCCATGT [SEQ ID NO:404]                                         - Oligo #352 Length: 000018                                                   - GGAGAGATTT TTAAGAAT [SEQ ID NO:405]                                         - Oligo #353 Length: 000018                                                   - AAAAATCTCA CCCCATGT [SEQ ID NO:406]                                         - Oligo #354 Length: 000018                                                   - GGTGAGATTT TTAAGAAT [SEQ ID NO:407]                                         - Oligo #355 Length: 000018                                                   - AAAAATCTCT ACCCATGT [SEQ ID NO:408]                                         - Oligo #356 Length: 000018                                                   - GTAGAGATTT TTAAGAAT [SEQ ID NO:409]                                         - Oligo #357 Length: 000027                                                   - CTGCCCCTGG CCACGGCCGC AGCTACG [SEQ ID NO:410]                               - Oligo #358 Length: 000024                                                   - ATGGATTGGA TGTCGCGTAG CTGC [SEQ ID NO:411]                                  - Oligo #359 Length: 000027                                                   - CTGCCCCTGG CCACGGCCGC AGGTACG [SEQ ID NO:412]                               - Oligo #360 Length: 000024                                                   - ATGGATTGGA TGTCGCGTAC CTGC [SEQ ID NO:413]                                  - Oligo #361 Length: 000027                                                   - CTGCCCCTGG CCACGGCCGC AATCACG [SEQ ID NO:414]                               - Oligo #362 Length: 000024                                                   - ATGGATTGGA TGTCGCGTGA TTGC [SEQ ID NO:415]                                  - Oligo #363 Length: 000021                                                   - GCTCATCCAA TCCATATCAA G [SEQ ID NO:416]                                     - Oligo #364 Length: 000024                                                   - ATGGATTGGA TGAGCCGTGG GTGC [SEQ ID NO:417]                                  - Oligo #365 Length: 000021                                                   - CAGCATCCAA TCCATATCAA G [SEQ ID NO:418]                                     - Oligo #366 Length: 000024                                                   - ATGGATTGGA TGCTGCGTGG GTGC [SEQ ID NO:419]                                  - Oligo #367 Length: 000021                                                   - CACCATCCAA TCCATATCAA G [SEQ ID NO:420]                                     - Oligo #368 Length: 000024                                                   - ATGGATTGGA TGGTGCGTGG GTGC [SEQ ID NO:421]                                  - Oligo #369 Length: 000021                                                   - AAACATCCAA TCCATATCAA G [SEQ ID NO:422]                                     - Oligo #370 Length: 000024                                                   - ATGGATTGGA TGTTTCGTGG GTGC [SEQ ID NO:423]                                  - Oligo #371 Length: 000021                                                   - CGAGCTCCAA TCCATATCAA G [SEQ ID NO:424]                                     - Oligo #372 Length: 000024                                                   - ATGGATTGGA GCTCGCGTGG GTGC [SEQ ID NO:425]                                  - Oligo #373 Length: 000021                                                   - CGAAACCCAA TCCATATCAA G [SEQ ID NO:426]                                     - Oligo #374 Length: 000024                                                   - ATGGATTGGG TTTCGCGTGG GTGC [SEQ ID NO:427]                                  - Oligo #375 Length: 000021                                                   - CGAGACCCAA TCCATATCAA G [SEQ ID NO:428]                                     - Oligo #376 Length: 000024                                                   - ATGGATTGGG TCTCGCGTGG GTGC [SEQ ID NO:429]                                  - Oligo #377 Length: 000021                                                   - CGAATCCCAA TCCATATCAA G [SEQ ID NO:430]                                     - Oligo #378 Length: 000024                                                   - ATGGATTGGG ATTCGCGTGG GTGC [SEQ ID NO:431]                                  - Oligo #379 Length: 000021                                                   - CGAAAACCAA TCCATATCAA G [SEQ ID NO:432]                                     - Oligo #380 Length: 000024                                                   - ATGGATTGGT TTTCGCGTGG GTGC [SEQ ID NO:433]                                  - Oligo #381 Length: 000021                                                   - CGAATGCCAA TCCATATCAA G [SEQ ID NO:434]                                     - Oligo #382 Length: 000024                                                   - ATGGATTGGC ATTCGCGTGG GTGC [SEQ ID NO:435]                                  - Oligo #383 Length: 000021                                                   - CGATTCCCAA TCCATATCAA G [SEQ ID NO:436]                                     - Oligo #384 Length: 000024                                                   - ATGGATTGGG AATCGCGTGG GTGC [SEQ ID NO:437]                                  - Oligo #385 Length: 000021                                                   - CGATCCCCAA TCCATATCAA G [SEQ ID NO:438]                                     - Oligo #386 Length: 000024                                                   - ATGGATTGGG GATCGCGTGG GTGC [SEQ ID NO:439]                                  - Oligo #387 Length: 000021                                                   - CGATGGCCAA TCCATATCAA G [SEQ ID NO:440]                                     - Oligo #388 Length: 000024                                                   - ATGGATTGGC CATCGCGTGG GTGC [SEQ ID NO:441]                                  - Oligo #389 Length: 000021                                                   - CGATACCCAA TCCATATCAA G [SEQ ID NO:442]                                     - Oligo #390 Length: 000024                                                   - ATGGATTGGG TATCGCGTGG GTGC [SEQ ID NO:443]                                  - Oligo #391 Length: 000034                                                   - CATCCAATCC AAATCAAGGA CGGTGACTGG AATG [SEQ ID NO:444]                       - Oligo #392 Length: 000044                                                   - AATTCATTCC AGTCACCGTC CTTGATTTGG ATTGGATGTC GCGT [SEQ ID NO:445]                                                   - Oligo #393 Length: 000034                                                   - CATCCAATCG AAATCAAGGA                                                     CGGTGACTGG AATG [SEQ ID NO:446]                                                 - Oligo #394 Length: 000044                                                   - AATTCATTCC AGTCACCGTC                                                     CTTGATTTCG ATTGGATGTC GCGT [SEQ                                               ID NO:447]                               - Oligo #395 Length: 000034                                                   - CATCCAATCA TGATCAAGGA CGGTGACTGG AATG [SEQ ID NO:448]                       - Oligo #396 Length: 000044                                                   - AATTCATTCC AGTCACCGTC CTTGATCATG ATTGGATGTC GCGT [SEQ ID NO:449]                                                   - Oligo #397 Length: 000034                                                   - CATCCAATCT TCATCAAGGA                                                     CGGTGACTGG AATG [SEQ ID NO:450]                                                 - Oligo #398 Length: 000044                                                   - AATTCATTCC AGTCACCGTC                                                     CTTGATGAAG ATTGGATGTC GCGT [SEQ                                               ID NO:451]                               - Oligo #399 Length: 000034                                                   - CATCCAATCT CCATCAAGGA CGGTGACTGG AATG [SEQ ID NO:452]                       - Oligo #400 Length: 000044                                                   - AATTCATTCC AGTCACCGTC CTTGATGGAG ATTGGATGTC GCGT [SEQ ID NO:453]                                                   - Oligo #401 Length: 000034                                                   - CATCCAATCg taATCAAGGA                                                     CGGTGACTGG AATG [SEQ ID NO:454]                                                 - Oligo #402 Length: 000044                                                   - AATTCATTCC AGTCACCGTC                                                     CTTGATTACG ATTGGATGTC GCGT [SEQ                                               ID NO:455]                               - Oligo #403 Length: 000021                                                   - CGACATCCAA TCCGTATCAA G [SEQ ID NO:456]                                     - Oligo #404 Length: 000024                                                   - ACGGATTGGA TGTCGCGTGG GTGC [SEQ ID NO:457]                                  - Oligo #405 Length: 000021                                                   - CGACATCCAA TCAAAATCAA G [SEQ ID NO:458]                                     - Oligo #406 Length: 000024                                                   - TTTGATTGGA TGTCGCGTGG GTGC [SEQ ID NO:459]                                  - Oligo #407 Length: 000021                                                   - CGACATCCAA TCTACATCAA G [SEQ ID NO:460]                                     - Oligo #408 Length: 000024                                                   - GTAGATTGGA TGTCGCGTGG GTGC [SEQ ID NO:461]                                  - Oligo #409 Length: 000016                                                   - GCTGGTGACT GGAATG [SEQ ID NO:462]                                           - Oligo #410 Length: 000026                                                   - AATTCATTCC AGTCACCAGC CTTGAT [SEQ ID NO:463]                                - Oligo #411 Length: 000016                                                   - AACGGTGACT GGAATG [SEQ ID NO:464]                                           - Oligo #412 Length: 000026                                                   - AATTCATTCC AGTCACCGTT CTTGAT [SEQ ID NO:465]                                - Oligo #413 Length: 000016                                                   - GAAGGTGACT GGAATG [SEQ ID NO:466]                                           - Oligo #414 Length: 000026                                                   - AATTCATTCC AGTCACCTTC CTTGAT [SEQ ID NO:467]                                - Oligo #415 Length: 000016                                                   - GGTGGTGACT GGAATG [SEQ ID NO:468]                                           - Oligo #416 Length: 000026                                                   - AATTCATTCC AGTCACCACC CTTGAT [SEQ ID NO:469]                                - Oligo #417 Length: 000016                                                   - ATCGGTGACT GGAATG [SEQ ID NO:470]                                           - Oligo #418 Length: 000026                                                   - AATTCATTCC AGTCACCGAT CTTGAT [SEQ ID NO:471]                                - Oligo #419 Length: 000016                                                   - CTGGGTGACT GGAATG [SEQ ID NO:472]                                           - Oligo #420 Length: 000026                                                   - AATTCATTCC AGTCACCCAG CTTGAT [SEQ ID NO:473]                                - Oligo #421 Length: 000016                                                   - TTCGGTGACT GGAATG [SEQ ID NO:474]                                           - Oligo #422 Length: 000026                                                   - AATTCATTCC AGTCACCGAA CTTGAT [SEQ ID NO:475]                                - Oligo #423 Length: 000016                                                   - TCCGGTGACT GGAATG [SEQ ID NO:476]                                           - Oligo #424 Length: 000026                                                   - AATTCATTCC AGTCACCGGA CTTGAT [SEQ ID NO:477]                                - Oligo #425 Length: 000032                                                   - AATTCGCTAG GAAACTGACG TTCTATCTGA AA [SEQ ID NO:478]                         - Oligo #426 Length: 000037                                                   - CTCAAGGGTT TTCAGATAGA ACGTCAGTTT CCTAGCG [SEQ ID NO:479]                    - Oligo #427 Length: 000032                                                   - AATTCCAGAG GAAACTGACG TTCTATCTGA AA [SEQ ID NO:480]                         - Oligo #428 Length: 000037                                                   - CTCAAGGGTT TTCAGATAGA ACGTCAGTTT CCTCTGG [SEQ ID NO:481]                    - Oligo #429 Length: 000032                                                   - AATTCCACAG GAAACTGACG TTCTATCTGA AA [SEQ ID NO:482]                         - Oligo #430 Length: 000037                                                   - CTCAAGGGTT TTCAGATAGA ACGTCAGTTT CCTGTGG [SEQ ID NO:483]                    - Oligo #431 Length: 000032                                                   - AATTCTCCAG GAAACTGACG TTCTATCTGA AA [SEQ ID NO:484]                         - Oligo #432 Length: 000037                                                   - CTCAAGGGTT TTCAGATAGA ACGTCAGTTT CCTGGAG [SEQ ID NO:485]                    - Oligo #433 Length: 000032                                                   - AATTCCGGAG GCGTCTGACG TTCTATCTGA AA [SEQ ID NO:486]                         - Oligo #434 Length: 000037                                                   - CTCAAGGGTT TTCAGATAGA ACGTCAGACG CCTCCGG [SEQ ID NO:487]                    - Oligo #435 Length: 000032                                                   - AATTCCGGAG GGAACTGACG TTCTATCTGA AA [SEQ ID NO:488]                         - Oligo #436 Length: 000037                                                   - CTCAAGGGTT TTCAGATAGA ACGTCAGTTC CCTCCGG [SEQ ID NO:489]                    - Oligo #437 Length: 000032                                                   - AATTCCGGAG GCACCTGACG TTCTATCTGA AA [SEQ ID NO:490]                         - Oligo #438 Length: 000037                                                   - CTCAAGGGTT TTCAGATAGA ACGTCAGGTG CCTCCGG [SEQ ID NO:491]                    - Oligo #439 Length: 000032                                                   - AATTCCGGAG GATCCTGACG TTCTATCTGA AA [SEQ ID NO:492]                         - Oligo #440 Length: 000037                                                   - CTCAAGGGTT TTCAGATAGA ACGTCAGGAT CCTCCGG [SEQ ID NO:493]                    - Oligo #441 Length: 000032                                                   - AATTCCGGAG GTCCCTGACG TTCTATCTGA AA [SEQ ID NO:494]                         - Oligo #442 Length: 000037                                                   - CTCAAGGGTT TTCAGATAGA ACGTCAGGGA CCTCCGG [SEQ ID NO:495]                    - Oligo #443 Length: 000032                                                   - AATTCCGGAG GAAACTGACG GACTATCTGA AA [SEQ ID NO:496]                         - Oligo #444 Length: 000037                                                   - CTCAAGGGTT TTCAGATAGT CCGTCAGTTT CCTCCGG [SEQ ID NO:497]                    - Oligo #445 Length: 000032                                                   - AATTCCGGAG GAAACTGACG ATCTATCTGA AA [SEQ ID NO:498]                         - Oligo #446 Length: 000037                                                   - CTCAAGGGTT TTCAGATAGA TCGTCAGTTT CCTCCGG [SEQ ID NO:499]                    - Oligo #447 Length: 000032                                                   - AATTCCGGAG GAAACTGACG CTGTATCTGA AA [SEQ ID NO:500]                         - Oligo #448 Length: 000037                                                   - CTCAAGGGTT TTCAGATACA GCGTCAGTTT CCTCCGG [SEQ ID NO:501]                    - Oligo #449 Length: 000032                                                   - AATTCCGGAG GAAACTGACG AAATATCTGA AA [SEQ ID NO:502]                         - Oligo #450 Length: 000037                                                   - CTCAAGGGTT TTCAGATATT TCGTCAGTTT CCTCCGG [SEQ ID NO:503]                    - Oligo #451 Length: 000032                                                   - AATTCCGGAG GAAACTGACG GTTTATCTGA AA [SEQ ID NO:504]                         - Oligo #452 Length: 000037                                                   - CTCAAGGGTT TTCAGATAAA CCGTCAGTTT CCTCCGG [SEQ ID NO:505]                    - Oligo #453 Length: 000032                                                   - AATTCCGGAG GAAACTGACG TTCTATCTGG CT [SEQ ID NO:506]                         - Oligo #454 Length: 000037                                                   - CTCAAGGGTA GCCAGATAGA ACGTCAGTTT CCTCCGG [SEQ ID NO:507]                    - Oligo #455 Length: 000032                                                   - AATTCCGGAG GAAACTGACG TTCTATCTGC GT [SEQ ID NO:508]                         - Oligo #456 Length: 000037                                                   - CTCAAGGGTA CGCAGATAGA ACGTCAGTTT CCTCCGG [SEQ ID NO:509]                    - Oligo #457 Length: 000032                                                   - AATTCCGGAG GAAACTGACG TTCTATCTGA AC [SEQ ID NO:510]                         - Oligo #458 Length: 000037                                                   - CTCAAGGGTG TTCAGATAGA ACGTCAGTTT CCTCCGG [SEQ ID NO:511]                    - Oligo #459 Length: 000032                                                   - AATTCCGGAG GAAACTGACG TTCTATCTGC AG [SEQ ID NO:512]                         - Oligo #460 Length: 000037                                                   - CTCAAGGGTC TGCAGATAGA ACGTCAGTTT CCTCCGG [SEQ ID NO:513]                    - Oligo #461 Length: 000032                                                   - AATTCCGGAG GAAACTGACG TTCTATCTGC AC [SEQ ID NO:514]                         - Oligo #462 Length: 000037                                                   - CTCAAGGGTG TGCAGATAGA ACGTCAGTTT CCTCCGG [SEQ ID NO:515]                    - Oligo #463 Length: 000032                                                   - AATTCCGGAG GAAACTGACG TTCTATCTGA TG [SEQ ID NO:516]                         - Oligo #464 Length: 000037                                                   - CTCAAGGGTC ATCAGATAGA ACGTCAGTTT CCTCCGG [SEQ ID NO:517]                    - Oligo #465 Length: 000032                                                   - AATTCCGGAG GAAACTGACG TTCTATCTGT TC [SEQ ID NO:518]                         - Oligo #466 Length: 000037                                                   - CTCAAGGGTG AACAGATAGA ACGTCAGTTT CCTCCGG [SEQ ID NO:519]                    - Oligo #467 Length: 000032                                                   - AATTCCGGAG GAAACTGACG TTCTATCTGT AC [SEQ ID NO:520]                         - Oligo #468 Length: 000037                                                   - CTCAAGGGTG TACAGATAGA ACGTCAGTTT CCTCCGG [SEQ ID NO:521]                    - Oligo #469 Length: 000040                                                   - CATGGCTAAC TGCTCTAACA TGATCGATGA AATTATAACA [SEQ ID NO:522]                 - Oligo #470 Length: 000036                                                   - CACTTAAAGC AGCCACCTTT GCCTTTGCTG GACTTC [SEQ ID NO:523]                     - Oligo #471 Length: 000027                                                   - AACAACCTCA ATGGGGAAGA CCAAGAT [SEQ ID NO:524]                               - Oligo #472 Length: 000045                                                   - CTTTAAGTGT GTTATAATTT CATCGATCAT GTTAGAGCAG TTAGC [SEQ ID NO:525]                                                  - Oligo #473 Length: 000036                                                   - GAGGTTGTTG AAGTCCAGCA                                                     AAGGCAAAGG TGGCTG [SEQ ID NO:526]        - Oligo #474 Length: 000018                                                   - ATCTTGGTCT TCCCCATT [SEQ ID NO:527]                                         - Oligo #475 Length: 000036                                                   - ATCCTGATGG AAAATAACCT TCGAAGGCCA AACCTG [SEQ ID NO:528]                     - Oligo #476 Length: 000024                                                   - GAGGCATTCA ACAGGGCTGT CAAG [SEQ ID NO:529]                                  - Oligo #477 Length: 000015                                                   - AGTTTACAGA ATGCA [SEQ ID NO:530]                                            - Oligo #478 Length: 000027                                                   - CCTTCGAAGG TTATTTTCCA TCAGGAT [SEQ ID NO:531]                               - Oligo #479 Length: 000024                                                   - CCTGTTGAAT GCCTCCAGGT TTGG [SEQ ID NO:532]                                  - Oligo #480 Length: 000020                                                   - TTCTGTAAAC TCTTGACAGC [SEQ ID NO:533]                                       - Oligo #481 Length: 000021                                                   - TCAGCAATTG AGAGCATTCT T [SEQ ID NO:534]                                     - Oligo #482 Length: 000018                                                   - AAAAATCTCC TGCCATGT [SEQ ID NO:535]                                         - Oligo #483 Length: 000048                                                   - CTGCCCCTGG CCACGGCCGC ACCCACGCGA CATCCAATCC ATATCAAG [SEQ ID NO:536]        - Oligo #484 Length: 000027                                                   - CTGCCCCTGG CCACGGCCGC ACCCACG [SEQ ID NO:537]                               - Oligo #485 Length: 000021                                                   - CGACATCCAA TCCATATCAA G [SEQ ID NO:538]                                     - Oligo #486 Length: 000016                                                   - GACGGTGACT GGAATG [SEQ ID NO:539]                                           - Oligo #487 Length: 000019                                                   - GCTCTCAATT GCTGATGCA [SEQ ID NO:540]                                        - Oligo #488 Length: 000018                                                   - CAGGAGATTT TTAAGAAT [SEQ ID NO:541]                                         - Oligo #489 Length: 000048                                                   - ATGGATTGGA TGTCGCGTGG GTGCGGCCGT GTGCGGCCGT AGACATGG [SEQ ID NO:542]        - Oligo #490 Length: 000024                                                   - GGCCGTGGCC AGGGGCAGAC ATGG [SEQ ID NO:543]                                  - Oligo #491 Length: 000024                                                   - ATGGATTGGA TGTCGCGTGG GTGC [SEQ ID NO:544]                                  - Oligo #492 Length: 000026                                                   - AATTCATTCC AGTCACCGTC CTTGAT [SEQ ID NO:545]                                - Oligo #493 Length: 000032                                                   - AATTCCGGAG GAAACTGACG TTCTATCTGA AA [SEQ ID NO:546]                         - Oligo #494 Length: 000032                                                   - ACCCTTGAGA ATGCGCAGGC TCAACAGTAA TA [SEQ ID NO:547]                         - Oligo #495 Length: 000037                                                   - CTCAAGGGTT TTCAGATAGA ACGTCAGTTT CCTCCGG [SEQ ID NO:548]                    - Oligo #496 Length: 000027                                                   - AGCTTATTAC TGTTGAGCCT GCGCATT [SEQ ID NO:549]                            __________________________________________________________________________

                                      TABLE 3                                     __________________________________________________________________________    POLYPEPTIDES                                                                  __________________________________________________________________________    PEPTIDE #1; pMON5988 (Example 9); (15-125)hIL-3                                         Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu [SEQ ID                                                NO:65]                                           15                  20                  25                             - Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly                        30                  35                  40                             - Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn                        45                  50                  55                             - Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser                        60                  65                  70                             - Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu                        75                  80                  85                             - Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly                        90                  95                  100                            - Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr                        105                 110                 115                            - Leu Glu Asn Ala Gln Ala Gln Gln                                                    120                 125                                                - PEPTIDE #A1; pMON13304 (Example 55); Met-Ala-(15-125)hIL-3 (98I,                                                 100R);                                  Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu [SEQ ID                                                NO:66]                                           15                  20                  25                             - Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly                        30                  35                  40                             - Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn                        45                  50                  55                             - Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser                        60                  65                  70                             - Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu                        75                  80                  85                             - Ala Thr Ala Ala Pro Thr Arg His Pro Ile Ile Ile Arg Asp Gly                        90                  95                 100                             - Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr                        105                 110                 115                            - Leu Glu Asn Ala Gln Ala Gln Gln                                                    120                 125                                                - PEPTIDE #A2; pMON13305 Met-Ala-(15-125)hIL-3; (95R, 98I, 100R); -                                               Met Ala Asn Cys Ser Asn Met Ile                                               Asp Glu Ile Ile Thr His Leu [SEQ                                              ID NO:67]                                        15                  20                  25                             - Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly                        30                  35                  40                             - Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn                        45                  50                  55                             - Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser                        60                  65                  70                             - Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu                        75                  80                  85                             - Ala Thr Ala Ala Pro Thr Arg Arg Pro Ile Ile Ile Arg Asp Gly                        90                  95                 100                             - Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr                        105                 110                 115                            - Leu Glu Asn Ala Gln Ala Gln Gln                                                    120                 125                                                - PEPTIDE #A3; pMON13286 Met-Ala-(15-125)hIL-3; (42D, 45M, 46S); - Met                                            Ala Asn Cys Ser Asn Met Ile Asp                                               Glu Ile Ile Thr His Leu [SEQ ID                                               NO:69]                                           15                  20                  25                             - Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Asp                                                              30                  35                                                             40                          - Glu Asp Met Ser Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn                        45                  50                  55                             - Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser                        60                  65                  70                             - Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu                        75                  80                  85                             - Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly                        90                  95                  100                            - Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr                        105                 110                 115                            - Leu Glu Asn Ala Gln Ala Gln Gln                                                    120                 125                                             __________________________________________________________________________

Polypeptides corresponding to SEQ ID NOS. 15, 16, 17, 18 and 129comprising (1-133)hIL-3 containing one or more amino acid substitutionscan be made using the procedures described above and in the followingexamples by starting with the appropriate oligonuctiotides and thenconstructing the DNA encoding the polypeptide and expressing it in anappropriate host cell. In a similar manner polypeptides which correspondto SEQ ID NOS. 19, 20, 21, 22 and 130 and contain one or more amino acidsubstitutions and wherein from 1 to 14 amino acids have beensequentially deleted from the N-terminus, or from 1 to 15 amino acidshave been deleted from the C-terminus or deletions of amino acids havebeen made from both the N-terminus and the C-terminus can also be madeby following the procedures described above and in the followingexamples, beginning with the appropriate starting materials.

Additional details may be found in U.S. patent application Ser. No.07/981,044 filed Nov. 24, 1992, which is hereby incorporated byreference in its entirety.

Additional details may be found in co filed United States PatentApplication Attorney docket number 2713/2, which is hereby incorporatedby reference in its entirety.

All references, patents or applications cited herein are incorporated byreference in their entirety.

Further details known to those skilled in the art may be found in T.Maniatis, et al., Molecular Cloning, A Laboratory Manual, Cold SpringHarbor Laboratory (1982) and references cited therein, incorporatedherein by reference in its entirety; and in J. Sambrook, et al.,Molecular Cloning, A Laboratory manual, 2nd edition, Cold Spring HarborLaboratory (1989) and references cited therein, incorporated herein byreference in its entirety.

The following examples will illustrate the invention in greater detailalthough it will be understood that the invention is not limited tothese specific examples.

Amino acids are shown herein by standard one letter or three letterabbreviations as follows:

    ______________________________________                                        Abbreviated Designation                                                                          Amino Acid                                                 ______________________________________                                        A           Ala        Alanine                                                CCysCysteine                                                                     - DAspAspartic acid                                                           - EGluGlutamic acid                                                           - FPhePhenylalanine                                                           - GGlyGlycine                                                                 - HHisHistidine                                                               - IIleIsoleucine                                                              - KLysLysine                                                                  - LLeuLeucine                                                                 - MMetMethionine                                                              - NAsnAsparagine                                                              - PProProline                                                                 - QGlnGlutamine                                                               - RArgArginine                                                                - SSerSerine                                                                  - TThrThreonine                                                               - VValValine                                                                  - WTrpTryptophan                                                              - YTyrTyrosine                                                             ______________________________________                                    

Various other examples will be apparent to the person skilled in the artafter reading the present disclosure without departing from the spiritand scope of the invention. It is intended that all such other examplesbe included within the scope of the appended claims.

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EXAMPLE 1 Construction of pMON 5846 (FIG. 4) which encodes[Met-(1-133)hIL-3 (Arg¹²⁹)]

A plasmid containing the gene for the cDNA of hIL-3 cloned into pUC18 onan EcoRI to HindIII fragment was obtained from British BiotechnologyLimited (Cambridge, England). This plasmid was designated pPO518. Thepurified plasmid DNA was cleaved by the restriction endonucleases NheIand BamHI. Approximately 0.5 micrograms of cleaved plasmid DNA wasligated to 1.0 picomoles of a pair of annealed oligonucleotides with thefollowing sequence:

    5'-CTAGCGATCTTTTAATAAGCTTG-3' [SEQ ID NO: 1]

    3'-GCTAGAAAATTATTCGAACCTAG-5' [SEQ ID NO: 2]

The ligation mixture was used to transform competent JM101 cells toampicillin resistance. Colonies were picked, and plasmid DNA waspurified and subjected to restriction enzyme analysis. An isolate wasidentified in which the above oligonucleotide sequence had replaced theportion of the gene that encodes the extreme C-terminus. Within the newsequence was a new stop codon, TAA, and a recognition site for theenzyme HindIII. The new plasmid was designated pMON5846.

EXAMPLE 2 (a) Construction of expression vector plasmid pMON2341

The plasmid pMON2341 was used to supply the particular replicon andexpression elements used for construction of many of the plasmids usedto produce hIL-3 and hIL-3 muteins in E. coli. These expression elementsare described in the materials and methods section. pMON2341 is derivedfrom pMON5515 (Olins et al., 1988) and from pMON2429. pMON2429 consistsof the phage mp18 (Yanisch-Perron et al., 1985) with a BclI fragmentcarrying the chloramphenicol acetyl transferase (cat) gene from pBR328(Covarrubias et al., 1981) inserted into the BamHI site. The cat gene inpMON2429 has been altered from that in pBR328 by site directedmutagenesis (Kunkel, 1985). The recognition sites for NcoI and EcoRIwhich occur in the native gene were altered so that these tworestriction enzymes no longer recognize these sites. The changes did notalter the protein specified by the gene. Also, an NcoI site wasintroduced at the N-terminus of the coding sequence so that it overlapsthe codon for initiator methionine.

The steps involved in construction of pMON2341 are listed below:

(1) The DNAs of pMON5515 and pMON2429 were treated with NcoI andHindIII. The fragments were ligated and used to transform competent E.coli to ampicillin resistance. From these colonies, some were identifiedthat were chloramphenicol resistant. From one of these colonies, plasmidDNA was isolated in which the rat atriopeptigen gene of pMON5515 hadbeen replaced by the NcoI to HindIII fragment containing the cat genefrom pMON2429. This fragment contains the recognition sites for severalrestriction enzymes in the portion derived from the multilinker regionof mp18. The new plasmid was designated pMON2412.

(2) pMON2412 was treated with the enzyme ClaI which cleaves at onelocation in the pBR327 derived portion of the DNA. The protruding endswere rendered blunt by treatment with Klenow in the presence ofnucleotide precursors. This DNA was mixed with an isolated 514 bp RsaIfragment derived from pEMBL8 (Dente et al., 1983). This RsaI fragmentcontains the origin of replication of phage f1. This ligation mixturewas used to transform competent E. coli cells to ampicillin resistance.Among the plasmid DNAs isolated from these cells was pMON5578. Thisplasmid has the structure of pMON2412 with the f1 origin region insertedinto the ClaI site. This is illustrated in the Figures and in Olins andRangwala (1990).

(3) The DNA of pMON5578 was treated with restriction enzymes HindIII andMstII. The DNA was then treated with Klenow enzyme in the presence ofnucleotide precursors to render the ends blunt. This treated DNA wasligated and used to transform competent E. coli to ampicillinresistance. From the ampicillin resistant colonies, one plasmid wasrecovered from which the portion between HindIII and MstII was absent.This deletion resulted in the removal of sequences from the plasmidwhich are recognized by a number of restriction endonuclease sites. Thenew plasmid was designated pMON5582.

(4) The DNA of pMON5582 was treated with SstII and BclI and ligated inthe presence of annealed oligonucleotides with the sequences shownbelow.

    5'-GGCAACAATTTCTACAAAACACTTGATACTGTATGAGCATACAGTATAATTGCTTCAACAGAACAGATC-3    '                                             [SEQ ID NO:3]                                                                           - 3'-CGCCGTTGTTAAA                                                          GATGTTTTGTGAACTATGAC                                                          ATACTCGTATGTCATATTAA                                                          CGAAGTTGTCTTGT-5'[SE                                                          Q ID NO:4]          

This sequence encodes the essential elements of the recA promoter of E.coli including the transcription start site and the lexA repressorbinding site (the operator) (Sancar et al., 1980). The plasmid recoveredfrom the ligation mixes contained this recA promoter in place of the onein pMON5582 (and in pMON5515). The functionality of the recA promoterwas illustrated by Olins and Rangwala (1990). The new plasmid wasdesignated pMON5594.

(5) To eliminate the single EcoRI site in pMON5594, the DNA was treatedwith EcoRI, then with Klenow in the presence of nucleotide precursors torender the ends blunt and then the DNA was ligated. From this ligationmix a plasmid was recovered whose DNA was not cleaved with EcoRI. Thisplasmid was designated pMON5630.

(6) To alter the single recognition site for PstI, plasmid pMON5630 wassubjected to site directed mutagenesis (Kunkel, 1985). Theoligonucleotide used in this procedure has the sequence shown below.

    5'-CCATTGCTGCCGGCATCGTGGTC-3' [SEQ ID NO:5]

The result of the procedure was to construct pMON2341 which differs frompMON5630 in that the PstI site in the beta-lactamase gene was altered sothat PstI no longer recognizes the site. The single nucleotide changedoes not alter the amino acid sequence of the beta-lactamase protein.

(b) Construction of pMON5847 (FIG. 5) which encodes[Met-(1-133)hIL-3(Arg¹²⁹)]

Plasmid pMON2341 was used to supply the replicon, promotor, ribosomebinding site, transcription terminator and antibiotic resistance markerfor the plasmids used to produce hIL-3 in E. coli from cDNA derivedhIL-3 genes.

Plasmid pMON2341 was treated with restriction enzymes NcoI and HindIII.The restriction fragment containing the replication origin was purified.The DNA of plasmid pMON5846 was treated with NcoI and HindIII. Therestriction fragment containing the hIL-3 gene was gel purified. Thesepurified restriction fragments were mixed and ligated. The ligationmixture was used to transform competent JM101 cells to ampicillinresistance. Colonies were picked, and plasmid DNA was purified andanalyzed using restriction enzymes. pMON5847 was identified as a plasmidwith the replicon of pMON2341 and the hIL-3 gene in place of thechloramphenicol acetyl transferase gene. JM101 cells harboring thisplasmid were cultured in M9 medium and treated with nalidixic acid asdescribed above. Samples of the culture were examined for proteincontent. It was found that this hIL-3 mutein was produced at about 6% oftotal cell protein as measured on Coomassie stained polyacrylamide gels.

EXAMPLE 3 Construction of pMON5854 (FIG. 7) which encodes[Met-(1-133)hIL-3(Arg¹²⁹)]

To increase the accumulation of hIL-3 in E. coli, the coding sequence ofthe amino terminal portion of the protein was altered to more closelyreflect the codon bias found in E. coli genes that produce high levelsof proteins (Gouy and Gautier, 1982). To change the coding sequence forthe amino terminal portion of the gene, a pair of syntheticoligonucleotides were inserted between the NcoI and HpaI sites withinthe coding sequence. About 0.5 micrograms of DNA of the plasmid pMON5847(Example 2) was treated with NcoI and HpaI. This DNA was mixed with anannealed pair of oligonucleotides with the following sequence:

                           [SEQ ID NO:6]                                             -                                                                          5'-CATGGCTCCAATGACTCAGACTACTTCTCTTAAGACTTCTTGGGTT-3'                             -                     [SEQ ID NO:7]                                           -                                                                          3'-CGAGGTTACTGAGTCTGATGAAGAGAATTCTGAAGAACCCAA-5'                          

The fragments were ligated. The ligation mixture was used to transformcompetent JM101 to ampicillin resistance. Colonies were picked intobroth. From the cultures plasmid DNA was made and examined for thepresence of a DdeI site (CTNAG) which occurs in the synthetic sequencebut not between the NcoI and HpaI sites in the sequence of pMON5847. Thenew recombinant plasmid was designated pMON5854. The nucleotide sequenceof the DNA in the coding sequence of the amino terminal portion of thehIL-3 gene in pMON5854 was determined by DNA sequencing and found to bethe same as that of the synthetic oligonucleotide used in ligation.Cultures of JM101 cells harboring this plasmid were grown and treatedwith nalidixic acid to induce production of the hIL-3 mutant protein.Analysis of the proteins on Coomassie gels showed that the accumulationof hIL-3 mutein was about 25% of total cell protein in culturesharboring pMON5854, significantly higher than it was in culturesharboring pMON5847.

EXAMPLE 4 Construction of pMON5887 (FIG. 12) which encodes[Met-(1-125)hIL-3]

The plasmid DNA of pMON5854 (Example 3) was treated with EcoRI andHindIII and the larger fragment was gel purified. About 0.5 microgram ofthis DNA was ligated to 1 picomole of an annealed pair ofoligonucleotides which encode amino acids 107 through 125 of hIL-3. Thesequences of these oligonucleotides are shown below.

    EcoRI to HindIII                                                                5'-AATTCCGTCGTAAACTGACCTTCTATCTGAAAACCTTGGAGAACGCGCAGGCTCAACAGTAATA-3'                                                         [SEQ ID NO:8]                 - 3'-GGCAGCATTTGACTGGAAGATAGACTTTTGGAACCTCTTGCGCGTCCGAGTTGTCATTATTCGA-5                                                       ' [SEQ ID NO:9]        

After ligation, the DNA was used to transform competent JM101 cells toampicillin resistance. Colonies were picked into broth and plasmid DNAwas isolated from each culture. Restriction analysis of the plasmid DNAshowed the presence of an EcoRI to HindIII fragment smaller than that ofpMON5854. The nucleotide sequence of the portion of the coding sequencebetween the EcoRI and HindIII sites was determined to confirm theaccuracy of the replaced sequence. The new plasmid was designatedpMON5887 encoding Met-(1-125)hIL-3 which has the following amino acidsequence:

                          [SEQ ID NO:10]                                             -                                                                          Met Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser                              - Trp Val Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr                         - His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn                         - Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn                         - Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala                         - Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile                         - Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala                         - Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp                         - Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys                         - Thr Leu Glu Asn Ala Gln Ala Gln Gln                                  

EXAMPLE 5 Construction of pMON5967 which encodes[Met-Ala-(15-125-)hIL-3]

Plasmid DNA of pMON5887 isolated from E. coli GM48 (dam-) was cleavedwith NcoI and ClaI and ligated to 1 picomole of an annealed pair ofoligonucleotides, Nco I and ClaI, encoding amino acids [Met Ala(15-20)hIL-3]. The sequence of these oligonucleotides is shown below.

    5'-CATGGCTAACTGCTCTAACATGAT-3'                                                                      [SEQ ID NO:11]                                             - 3'-CGATTGACGAGATTGTACTAGC-5' [SEQ ID NO:12]                          

The resulting ligation mix was used to transform competent E. coli JM101cells to ampicillin resistant colonies. Plasmid DNA was isolated fromthese cells and the size of the inserted fragment was determined to besmaller than that of pMON5887 by restriction analysis using NcoI andNsiI. The nucleotide sequence of the region between NcoI and ClaI wasdetermined and found to be that of the synthetic oligonucleotides. Thenew plasmid was designated pMON5967 and cells containing it were inducedfor protein production. Sonicated cell pellets and supernatants wereused for protein purification and bio-assay.

EXAMPLE 6 Construction of pMON5978 which encodes [Met-Ala-(15-125)hIL-3]

Plasmid DNA of pMON5967 isolated from E. coli GM48(dam-) was cleavedwith ClaI and NsiI and ligated to 1 picomole of an annealed assembly ofsix oligonucleotides encoding hIL-3 amino acids 20-70 (FIG. 2). Thissynthetic fragment encodes three unique restriction sites, EcoRV, XhoIand PstI. The sequence of these oligonucleotides is shown in FIG. 2.

The resulting ligation mix was used to transform competent E. coli JM101cells to ampicillin resistant colonies. Plasmid DNA was isolated andscreened with XbaI and EcoRV for the presence of the new restrictionsite EcoRV. The DNA sequence of the region between ClaI and NsiI wasdetermined and found to be the same as that of the syntheticoligonucleotides. The new plasmid was designated pMON5978, and cellscontaining it were induced for protein production. Sonicated cellpellets and supernatants were used for protein purification andbio-assay.

Plasmid pMON5978 encodes [Met-Ala-(15-125)hIL-3] which has the followingamino acid sequence:

                          [SEQ ID NO:13]                                             -                                                                          Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr                              - His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn                         - Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn                         - Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala                         - Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile                         - Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala                         - Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp                         - Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys                         - Thr Leu Glu Asn Ala Gln Ala Gln Gln                                  

EXAMPLE 7 Construction of pMON5898

Plasmid pMON5851 DNA was digested with restriction enzymes HindIII andNcoI resulting in a 3695 base pair NcoI, HindIII fragment. The geneticelements derived from pMON5851 are the beta-lactamase gene (AMP), pBR327origin of replication, phage f1 origin of replication as thetranscription terminator, AraBAD promoter, g10L ribosome binding siteand the lamb secretion leader. The AraBAD promoter is identical to thatdescribed in plasmid pMON6235 and the lamB signal peptide sequence usedis that shown in FIG. 8 fused to hIL-3 at the NcoI recognition site.Plasmid pMON5873 DNA was digested with restriction enzymes HindIII andNcoI resulting in a 408 base pair NcoI,HindIII fragment. The geneticelement derived from pMON5873 is the hIL-3 gene (1-133). Clonescontaining the hIL-3 (1-133) gene contained a 408 base pair NcoI,HindIII restriction fragment. This construct was designated pMON5898.

EXAMPLE 8 Construction of pMON5987

Plasmid pMON6458 DNA was digested with restriction enzymes NcoI andHindIII, resulting in a 3940 base pair NcoI,HindIII fragment. Thegenetic elements derived from pMON6458 are the beta-lactamase gene(AMP), pBR327 origin of replication, phage f1 origin of replication asthe transcription terminator, AraBAD promoter, g10L ribosome bindingsite and lamB secretion leader. Plasmid pMON5978 DNA was digested withNcoI and NsiI. The resulting 170 base pair NcoI, NsiI fragment encodesamino acids 15-71 of (15-125)hIL-3. Plasmid pMON5976 DNA was digestedwith NsiI and HindIII. The resulting 175 base pair NsiI,HindIII fragmentencodes amino acids 72-125 of (15-125)hIL-3. The restriction fragmentswere ligated, and the ligation reaction mixture was used to transform E.coli K-12 strain JM101. Transformant bacteria were selected onampicillin-containing plates. Plasmid DNA was isolated and screened forthe restriction sites EcoRV and NheI and DNA sequenced to confirm thecorrect insert.

EXAMPLE 9 Construction of pMON5988

The plasmid DNA of pMON5987 was digested with NheI and EcoRI, resultingin a 3903 base pair NheI, EcoRI fragment. The 3903 base pair NheI, EcoRIfragment was ligated to 1.0 picomoles of the following annealedoligonucleotides (Oligo #3 and Oligo #4):

    5'-CTAGCCACGGCCGCACCCACGCGACATCCAATCCATATCAAGGACGGTGACTGGAATG-3'                                                     [SEQ ID NO:131]                           - 3'-GGTGCCGGCGTGGGTGCGCTGTAGGTTAGGTATAGTTCCTGCCACTGACCTTACAATT-5'                                                          [SEQ ID NO:132]          

The ligation reaction mixture was used to transform E. coli K-12 strainJM101 and transformant bacteria were selected on ampicillin-containingplates. Plasmid DNA was isolated and sequenced to confirm positiveclones. This plasmid was constructed to change alanine 101 to asparticacid in the hIL-3 gene (15-125). The Ala¹⁰¹ to Asp¹⁰¹ change wasconfirmed by DNA sequencing. This plasmid was designated pMON5988 andencodes Peptide #1 [SEQ ID NO:65].

EXAMPLE 10 Construction of pMON5873 which Encodes [Met-(1-133)hIL-3]

The gene obtained from British Biotechnology, Ltd. specified arginine atcodon position 129. The amino acid specified in the native hIL-3 cDNA isserine. To produce a protein with the native sequence at this position,the portion of the coding sequence between the EcoRI site at codons 106and 107 and the NheI site at codons 129 and 130 was replaced. PlasmidDNA of pMON5854 (Example 3) and pMON5853 (Example 64) were treated withEcoRI and NheI. The larger fragments of each were gel purified. Thesewere ligated to a pair of an annealed oligonucleotides with thefollowing sequences:

    5'-AATTCCGTCGTAAACTGACCTTCTATCTGAAAACCTTGGAGAACGCGCAGGCTCAACAGACCACTCTGTCG    -3'                                            [SEQ ID NO: 136]                                                                          - 3'-GGCAGCATTT                                                             GACTGGAAGATAGACTT                                                             TTGGAACCTCTTGCGCG                                                             TCCGAGTTGTCTGGTGA                                                             GACAGCGATC-5'                                                                 [SEQ ID NO: 137] 

The ligation reaction mixtures were used to transform competent JM101cells to ampicillin resistance. Colonies were picked into broth andgrown. Plasmid DNA was isolated and screened for the presence of a newStyI recognition site present in the synthetic DNA and not in pMON5854and pMON5853. The nucleotide sequence of the gene in the region betweenEcoRI and NheI was determined and found to be that of the syntheticoligonucleotides. The new plasmids were designated pMON5873 encoding[Met-(1-133)hIL-3] and pMON5872 encoding [Met-(15-133)hIL-3].

The plasmid, pMON5873, encodes Met-(1-133)hIL-3 which has the followingamino acid sequence:

                         [SEQ ID NO:128]                                             -                                                                          Met Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser                              - Trp Val Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr                         - His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn                         - Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn                         - Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala                         - Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile                         - Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala                         - Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp                         - Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys                         - Thr Leu Glu Asn Ala Gln Ala Gln Gln Thr Thr Leu Ser                         - Leu Ala Ile Phe                                                      

EXAMPLE 11 Construction of pMON6458

Plasmid pMON6525 DNA was digested with restriction enzymes HindIII andSalI and the resulting 3172 base pair fragment was isolated from a 1%agarose gel by interception onto DEAE membrane. The genetic elementsderived from pMON6525 are the beta-lactamase gene (AMP), pBR327 originof replication, and phage f1 origin of replication as the transcriptionterminator. (The genetic elements derived from plasmid pMON6525 areidentical to those in plasmid pMON2341 which could also be used toconstruct pMON6458.) Plasmid pMON6457 was digested with restrictionenzymes HindIII and SalI and the resulting 1117 base pair fragment wasisolated by PAGE and crush and soak elution. The genetic elementsderived from pMON6457 are the pAraBAD promoter, g10L ribosome bindingsite, lamB secretion leader and the (15-125) hIL-3 gene. The restrictionfragments were ligated and the ligation reaction mixture was used totransform E. coli K-12 strain JM101. Transformant bacteria were selectedon ampicillin-containing plates. Plasmid DNA was isolated and the sizeof the inserted fragment was determined by restriction analysisemploying restriction enzymes NcoI and HindIII in double digest. Clonescontaining the hIL-3 gene (encoding amino acids 15-125) contained a 345base pair NcoI, HindIII restriction fragment. This construct wasdesignated pMON6458. This plasmid was constructed to eliminate an EcoRIrestriction site outside the hIL-3 gene coding region in plasmidpMON6457.

EXAMPLE 12 Construction of pMON6455

Plasmid pMON5905 DNA was digested with restriction enzymes HindIII andNcoI resulting in a 3936 base pair fragment. The genetic elementsderived from pMON5905 are the beta-lactamase gene (AMP), pBR327 originof replication, pAraBAD promoter, g10L ribosome binding site, lamBsecretion leader and phage f1 origin of replication as the transcriptionterminator. The following genetic elements; beta-lactamase gene (AMP),pBR327 origin of replication, g10L ribosome binding site and phage f1origin of replication as the transcription terminator, derived fromplasmid pMON5905 are identical to those in plasmid pMON5594 which couldalso be used to construct pMON6455. The AraBAD promoter is identical tothat described in pMON6235. The lamB signal peptide sequence used inpMON6455 is that shown in FIG. 8 fused to hIL-3 (15-125) at the NcoIsite. Plasmid pMON5887 DNA was digested with restriction enzymes HindIIIand NcoI, resulting in a 384 base pair NcoI, HindIII fragment. Therestriction fragments were ligated, and the ligation reaction mixturewas used to transform into E. coli K-12 strain JM101. Transformantbacteria were selected on ampicillin-containing plates. Plasmid DNA wasisolated and the size of the inserted fragment was determined byrestriction analysis employing restriction enzymes NcoI and HindIII indouble digest. Positive clones containing the hIL-3 gene (encoding aminoacids 1-125) contained a 384 base pair NcoI, HindIII restrictionfragment. This construct was designated pMON6455.

EXAMPLE 13 Construction of pMON6456

Plasmid pMON5905 DNA was digested with restriction enzymes HindIII andNcoI resulting in a 3936 base pair fragment. The genetic elementsderived from pMON5905 are the beta-lactamase gene (AMP), pBR327 originof replication, phage f1 origin of replication as the transcriptionterminator, pAraBAD promoter, g10L ribosome binding site and the lamBsecretion leader. Plasmid pMON5871 was digested with restriction enzymesHindIII and NcoI, resulting in a 330 base pair NcoI, HindIII fragment.The genetic element derived from pMON5871 encompassed the bases encodingthe (1-107) hIL-3 gene. The restriction fragments were ligated, and theligation reaction mixture was used to transform E. coli K-12 strainJM101. Transformant bacteria were selected on ampicillin-containingplates. Plasmid DNA was isolated and the size of the inserted fragmentwas determined by restriction analysis employing restriction enzymesNcoI and HindIII in double digest. Clones containing the hIL-3 gene(encoding amino acids 1-107) contained a 330 base pair NcoI, HindIIIrestriction fragment. This construct was designated pMON6456.

EXAMPLE 14 Construction of pMON6457

Plasmid pMON6455 DNA grown in E. coli strain GM48 (dam-) was digestedwith restriction enzymes NcoI and ClaI, resulting in a 4263 base pairNcoI, ClaI fragment. The restriction fragment was ligated to 1.0picomoles of annealed oligonucleotides (Oligo #5 and Oligo #6) with thefollowing sequence coding for Met Ala 14-20 hIL-3:

    5'-CATGGCTAACTGCTCTAACATGAT-3'                                                                      [SEQ ID NO:151]                                            - 3'-CGATTGACGAGATTGTACTAGC-5' [SEQ ID NO:152]                         

The resulting DNA was transformed into E. coli K-12 strain JM101 andtransformant bacteria were selected on ampicillin-containing plates.Plasmid DNA was isolated and the size of the inserted fragment wasdetermined by restriction analysis employing restriction enzymes XbaIand EcoRI in double digest. Positive clones containing the hIL-3 gene(encoding aa 15-125 of hIL-3) contained a 433 base pair XbaI, EcoRIrestriction fragment and were DNA sequenced. This construct wasdesignated pMON6457. This plasmid was constructed to delete the first 14amino acids of hIL-3. The coding sequence of the resulting gene beginsas follows:

    5'    ATG GCT AAC TGC...     3'[SEQ ID NO:153]                                   -       Met Ala Asn Cys...       [SEQ ID NO:154]                                            15                                                       

The first two amino acids (Methionine, Alanine) create an NcoIrestriction site and a signal peptidase cleavage site between the lamBsignal peptide and (15-125) hIL-3. Plasmid pMON6457 encodes (15-125)hIL-3 which has the amino acid sequence designated SEQ ID NO:65.

EXAMPLE 15 Construction of pMON6235

One of the DNA fragments used to create this plasmid was generated bysite-directed mutagenesis employing PCR techniques described previouslyusing the following oligonucleotides, Oligo #51(A) [SEQ ID NO:155] andOligo #52(A) [SEQ ID NO:156], were used as primers in this procedure.The template for the PCR reaction was E. coli strain W3110 chromosomalDNA, prepared as described in Maniatis (1982). The oligonucleotideprimers were designed to amplify the AraBAD promoter (Greenfield et al.,1978). The resulting DNA product was digested with the restrictionenzymes SacII and BglII. The reaction mixture was purified as describedpreviously. Plasmid, pMON5594, DNA was digested with SacII and BglII,resulting in a 4416 base pair SacII,BglII restriction fragment whichcontains the following genetic elements; beta-lactamase gene (AMP),pBR327 origin of replication, G10L ribosome binding site, phage f1origin of replication as the transcription terminator and thechloramphenicol acetyl transferase (cat) gene. The 4416 base pairSacII,BglII restriction fragment from pMON5594 was ligated to thePCR-generated SacII, BglII DNA fragment. The ligation mixture was usedto transform E. coli K-12 strain JM101. Positive clones contained a 323base pair SacII,BglII fragment and were DNA sequenced to confirm thatthe SacII,BglII fragment was the AraBAD promoter. This construct wasdesignated pMON6235.

EXAMPLE 16 Construction of pMON6460

One of the DNA fragments to construct this plasmid was generated bysite-directed mutagenesis employing PCR techniques described previouslyusing the oligonucleotides, Oligo #7 [SEQ ID NO: 26] and Oligo #8 [SEQID NO: 27] as primers. The template for the PCR reaction was plasmidpMON6458 DNA. The resulting DNA product was digested with therestriction enzymes NcoI and EcoRI. Upon completion, the digest washeated at 70° C. for 15 minutes to inactivate the enzymes. Therestriction fragment was purified by phenol/chloroform extraction andprecipitation with equal volume isopropanol in the presence of 2M NH₄OAc. The oligonucleotide, Oligo #8, introduces two stop codons (TAA)after amino acid 93 of hIL-3 and creates a SalI restriction endonucleaserecognition sequence. The NcoI, EcoRI restriction fragment from pMON6458was ligated to the PCR-generated NcoI, EcoRI restriction fragment.Positive clones containing the above mentioned changes released a 1023base pair SalI fragment. This construct was designated pMON6460. Thisplasmid was constructed to serve as the template for the creation ofsingle amino acid substitution variants at positions 94, 95, 96 and 97of hIL-3.

EXAMPLE 17 Construction of pMON6461

One of the DNA fragments to create this plasmid was generated bysite-directed mutagenesis employing PCR techniques described previouslyusing the following oligonucleotide, Oligo #7 [SEQ. ID NO: 26] and Oligo#9 [SEQ. ID NO: 28], as primers. The template for the PCR reaction wasplasmid pMON6458 DNA. The resulting DNA product was digested with therestriction enzymes NcoI and EcoRI. The oligonucleotide, Oligo #9,introduces two stop codons (TAA) after amino acid 97 of hIL-3 andcreates a SalI restriction endonuclease recognition sequence. The NcoI,EcoRI restriction fragment from pMON5458 was ligated to thePCR-generated NcoI, EcoRI DNA fragment. Positive clones containing theabove mentioned changes released a 1035 base pair SalI fragment. Thisconstruct was designated pMON6461. This plasmid was constructed to serveas the template for the creation of single amino acid substitutionvariants at positions 98, 99, 100 and 101 of hIL-3.

EXAMPLE 18 Construction of pMON6462

One of the DNA fragments to create this plasmid was generated bysite-directed mutagenesis employing PCR techniques described previouslyusing the following oligonucleotide, Oligo #7 [SEQ. ID NO: 26] and Oligo#10 [SEQ. ID NO: 31], as primers. The template for the PCR reaction wasplasmid pMON6458 DNA. The resulting DNA product was digested with therestriction enzymes NcoI and EcoRI. The oligonucleotide, Oligo #10 [SEQ.ID NO: 31] introduces two stop codons (TAA) after amino acid 101 ofhIL-3 and creates a SalI restriction endonuclease recognition sequence.The NcoI, EcoRI restriction fragment from pMON5458 was ligated to thePCR-generated NcoI, EcoRI DNA fragment. Positive clones containing theabove mentioned changes released a 1047 base pair SalI fragment. Thisconstruct was designated pMON6462. This plasmid was constructed to serveas the template for the creation of single amino acid substitutionvariants at positions 102, 103, 104 and 105 of hIL-3.

EXAMPLE 19 Construction of Single Amino Acid Substitution Libraries atPositions 94, 95, 96 and 97

One of the DNA fragments used to construct the plasmids containingsingle amino acid substitution at positions 94, 95, 96 and 97 wasgenerated by site-directed mutagenesis employing PCR techniquesdescribed previously. In the PCR reaction plasmid pMON6460 DNA was thetemplate and the oligonucleotide, Oligo #7 [SEQ. ID NO: 26], was used asthe primer at the N-terminus. The degenerate oligonucleotides, Oligo #11[SEQ. ID NO: 32], Oligo #12 [SEQ. ID NO: 33], Oligo #13 [SEQ. ID NO: 34]and Oligo #14 [SEQ. ID NO: 35], were the primers at the C-terminus.These oligonucleotides are 32-fold degenerate, with G, A, T or C in thefirst and second positions and G or C in the third position of a singlecodon at amino acid positions 94, 95, 96 and 97 of hIL-3 respectively.These degenerate oligonucleotide primers theoretically contain 32different codons encoding all 20 amino acid substitutions and onetranslational stop codon at a single position. The degenerateoligonucleotides (Oligo #11 [SEQ. ID NO: 32], Oligo #12 [SEQ. ID NO:33], Oligo #13 [SEQ. ID NO: 34] and Oligo #14 [SEQ. ID NO: 35]) replacethe twelve bases introduced into pMON6460, that encode the two stopcodons (TAA) after amino acid 93 of hIL-3 and the SalI recognitionsequence. At the other 9 bases the DNA sequence was restored to encodethe native hIL-3 protein sequence. The resulting PCR-generated DNAproducts were digested with the restriction enzymes NcoI and EcoRI. The4008 bp NcoI, EcoRI restriction fragment from pMON6460 was ligated tothe PCR-generated NcoI, EcoRI DNA fragments. Plasmid DNA from individualcolonies was isolated as described previously and screened by DNA dotblot differential hybridization using the oligonucleotide, Oligo #15[SEQ. ID NO: 36], as the probe which had been labeled with p³². Clonesshown to be positive by hybridization were selected, plasmid DNAisolated and DNA sequenced to determine the amino acid substitution.

EXAMPLE 20 Construction of Single Amino Acid Substitution Libraries atPositions 98, 99, 100 and 101

Single amino acid substitutions variants were constructed at position98, 99, 100 and 101 as described previously, with the following changes.In the PCR reaction the template was plasmid pMON6461 DNA and theoligonucleotide, Oligo #7 [SEQ. ID NO: 26], was used as the primer atthe N-terminus. The degenerate oligonucleotides, Oligo #16 [SEQ. ID NO:37], Oligo #17 [SEQ. ID NO: 38], Oligo #18 [SEQ. ID NO: 39] and Oligo#19 [SEQ. ID NO: 40], were used as primers at the C-terminus. Theresulting PCR-generated DNA products were purified and digested withrestriction enzymes NcoI and EcoRI. The 4008 bp NcoI, EcoRI restrictionfragment from pMON6461 was ligated to the PCR-generated DNA NcoI, EcoRIrestriction fragment. Single colonies were screened by DNA dot blotdifferential hybridization using the oligonucleotide, Oligo #20 [SEQ. IDNO: 41], as the probe. Clones shown to be positive by hybridization wereselected, plasmid DNA isolated and DNA sequenced to determine the aminoacid substitution.

EXAMPLE 21 Construction of Single Amino Acid Substitution Libraries atPositions 102, 103, 104 and 105

Single amino acid substitutions variants were constructed at position102, 103, 104 and 105 as described previously, with the followingchanges. The template was pMON6462 and the oligonucleotide, Oligo #7[SEQ. ID NO: 26], was used as the primer at the N-terminus. Thedegenerate oligonucleotides, Oligo #21 [SEQ. ID NO: 42], Oligo #22 [SEQ.ID NO: 43], Oligo #23 [SEQ. ID NO: 44] and Oligo #24 [SEQ. ID NO: 45]were used as primers at the C-terminus. The resulting PCR-generated DNAproducts were purified and digested with restriction enzymes, NcoI andEcoRI. The 4008 bp NcoI, EcoRI restriction fragment from pMON6462 wasligated to the PCR-generated NcoI, EcoRI restriction fragment. Singlecolonies were screened by DNA dot blot differential hybridization usingthe oligonucleotide, Oligo #25 [SEQ. ID NO: 46], as the probe. Clonesshown to be positive by hybridization were selected, plasmid DNAisolated and DNA sequenced to determine the amino acid substitution.

EXAMPLE 22 Construction of Plasmid pMON6464

Amino acids 17-22 of hIL-3 were deleted using site-directed PCRmutagenesis methods described previously. Plasmid pMON6458 DNA was thetemplate in the PCR reaction using the oligonucleotides, Oligo #26 andOligo #27 as primers. The resulting PCR-generated DNA products werepurified and digested with NcoI and EcoRI. The 4008 bp NcoI, EcoRIrestriction fragment from pMON6458 was ligated to the PCR-generatedNcoI, EcoRI restriction fragment. Positive clones contained a 263 basepair NcoI, EcoRI restriction fragment in which the bases encoding aminoacids 17-22 of hIL-3 have been deleted. pMON6464 was made to serve asthe template for the creation of single amino acid substitution variantsat positions 17, 18, 19, 20, 21 and 22 of hIL-3.

EXAMPLE 23 Construction of Plasmid pMON6465

Amino acids 23-28 of hIL-3 were deleted using site-directed PCRmutagenesis methods described previously. Plasmid pMON6458 DNA was thetemplate in the reaction using the oligonucleotides, Oligo #26 and Oligo#28, as primers. The resulting PCR-generated DNA product was purifiedand digested with NcoI and EcoRI. The 4008 bp NcoI, EcoRI restrictionfragment from pMON6458 was ligated to the PCR-generated NcoI, EcoRIrestriction fragment. Positive clones contained a 263 base pair NcoI,EcoRI restriction fragment in which the bases encoding amino acids 23-28of hIL-3 have been deleted. pMON6465 was made to serve as the templatefor the creation of single amino acid substitution variants at positions23, 24, 25, 26, 27 and 28 of hIL-3.

EXAMPLE 24 Construction of Plasmid pMON6466

Amino acids 29-34 of hIL-3 were deleted using site-directed PCRmutagenesis methods described previously. Plasmid pMON6458 DNA was thetemplate in the reaction using the oligonucleotides, Oligo #26 and Oligo#29 as the primers. The resulting PCR-generated DNA product was purifiedand digested with NcoI and EcoRI. The 4008 bp NcoI, EcoRI restrictionfragment from pMON6458 was ligated to the PCR-generated NcoI, EcoRIrestriction fragment. Positive clones contained a 263 base pair NcoI,EcoRI restriction fragment in which the bases encoding amino acids 29-34of hIL-3 have been deleted. pMON6466 was made to serve as the templatefor the creation of single amino acid substitution variants at positions29, 30, 31, 32, 33 and 34 of hIL-3.

EXAMPLE 25 Construction of Plasmid pMON6467

Amino acids 35-40 of hIL-3 were deleted using site-directed PCRmutagenesis methods described previously. Plasmid pMON5988 DNA was thetemplate in the reaction using the oligonucleotides, Oligo #7 and Oligo#30, as primers. The resulting PCR-generated DNA product was purifiedand digested with NcoI and EcoRV. The NcoI, EcoRV restriction fragmentfrom pMON5988 was ligated to the PCR-generated NcoI, EcoRV restrictionfragment. Positive clones contained a 81 base pair NcoI, EcoRVrestriction fragment in which the bases encoding amino acids 35-40 ofhIL-3 have been deleted. pMON6467 was made to serve as the template forthe creation of single amino acid substitution variants at positions 35,36, 37, 38, 39 and 40 of hIL-3.

EXAMPLE 26 Construction of Plasmid pMON6468

Amino acids 41-46 of hIL-3 were deleted using site-directed PCRmutagenesis methods described previously. Plasmid pMON5988 DNA was thetemplate in the reaction using the oligonucleotides, Oligo #7 and Oligo#31, as the primers. The resulting PCR-generated DNA product waspurified and digested with NcoI and XhoI. The NcoI, XhoI restrictionfragment from pMON5988 was ligated to the PCR-generated NcoI, XhoIrestriction fragment. Positive clones contained a 119 base pair NcoI,XhoI restriction fragment in which the bases encoding amino acids 41-46of hIL-3 have been deleted. pMON6468 was made to serve as the templatefor the creation of single amino acid substitution variants at positions41, 42, 43, 44, 45 and 46 of hIL-3.

EXAMPLE 27 Construction of Plasmid pMon6469

Amino acids 47-52 of hIL-3 were deleted using site-directed PCRmutagenesis methods described previously. Plasmid pMON5988 DNA was thetemplate in the reaction using the oligonucleotides, Oligo #7 and Oligo#32, as the primers. The resulting PCR-generated DNA product waspurified and digested with NcoI and XhoI. The NcoI, XhoI restrictionfragment from pMON5988 was ligated to the PCR-generated NcoI, XhoIrestriction fragment. Positive clones contained a 119 base pair NcoI,XhoI restriction fragment in which the bases encoding amino acids 47-52of hIL-3 have been deleted. pMON6469 was made to serve as the templatefor the creation of single amino acid substitution variants at positions47, 48, 49, 50, 51 and 52 of hIL-3.

EXAMPLE 28 Construction of Plasmid pMON6470

Amino acids 53-58 of hIL-3 were deleted using site-directed PCRmutagenesis methods described previously. Plasmid, pMON5988, DNA was thetemplate in the reaction using the oligonucleotides, Oligo # 7 and Oligo#33, as primers. The resulting PCR-generated DNA product was purifiedand digested with NcoI and NsiI. The NcoI, NsiI restriction fragmentfrom pMON5988 was ligated to the PCR-generated NcoI, NsiI restrictionfragment. Positive clones contained a 152 base pair NcoI, NsiIrestriction fragment in which the bases encoding amino acids 53-58 ofhIL-3 have been deleted. pMON6470 was made to serve as the template forthe creation of single amino acid substitution variants at positions 53,54, 55, 56, 57 and 58 of hIL-3.

EXAMPLE 29 Construction of Plasmid pMON6471

Amino acids 59-64 of hIL-3 were deleted using site-directed PCRmutagenesis methods described previously. Plasmid pMON5988 DNA was thetemplate in the reaction using the oligonucleotides, Oligo #7 and Oligo#34, as the primers. The resulting PCR-generated DNA product waspurified and digested with NcoI and NsiI. The NcoI, NsiI restrictionfragment from pMON5988 was ligated to the PCR-generated NcoI, NsiIrestriction fragment. Positive clones contained a 152 base pair NcoI,NsiI restriction fragment in which the bases encoding amino acids 59-64of hIL-3 have been deleted. pMON6471 was made to serve as the templatefor the creation of single amino acid substitution variants at positions59, 60, 61, 62, 63 and 64 of hIL-3.

EXAMPLE 30 Construction of Plasmid pMon6472

Amino acids 65-70 of hIL-3 were deleted using site-directed PCRmutagenesis methods described previously. Plasmid pMON5988 DNA was thetemplate in the reaction using the oligonucleotides, Oligo #26 and Oligo# 35, as primers. The resulting PCR-generated DNA product was purifiedand digested with EcoRI and XhoI. The EcoRI, XhoI restriction fragmentfrom pMON5988 was ligated to the PCR-generated EcoRI, XhoI restrictionfragment. Positive clones contained a 126 base pair EcoRI, XhoIrestriction fragment in which the bases encoding amino acids 65-70 ofhIL-3 have been deleted. pMON6472 was made to serve as the template forthe creation of single amino acid substitution variants at positions 65,66, 67, 68, 69 and 70 of hIL-3.

EXAMPLE 31 Construction of Plasmid pMON6473

Amino acids 71-76 of hIL-3 were deleted using site-directed PCRmutagenesis methods described previously. Plasmid, pMON5988, DNA was thetemplate in the reaction using the oligonucleotides, Oligo #26 and Oligo#36, as primers. The resulting PCR-generated DNA product was anddigested with PstI and EcoRI. The PstI, EcoRI restriction fragment frompMON5988 was ligated to the PCR-generated PstI, EcoRI restrictionfragment. Restriction analysis was with NcoI, NsiI and EcoRI in a tripledigest. Positive clones contained a 263 base pair NcoI, EcoRIrestriction fragment, in which the bases encoding amino acids 71-76 ofhIL-3 have been deleted, and lost the NsiI restriction site. pMON6473was made to serve as the template for the creation of single amino acidsubstitution variants at positions 71, 72, 73, 74, 75 and 76 of hIL-3.

EXAMPLE 32 Construction of Plasmid pMON6474

Amino acids 77-82 of hIL-3 were deleted using site-directed PCRmutagenesis methods described previously. Plasmid pMON5988 DNA was thetemplate in the reaction using the oligonucleotides, Oligo #26 and Oligo#37, as primers. The resulting PCR-generated DNA product was purifiedand digested with PstI and EcoRI. The PstI, EcoRI restriction fragmentfrom pMON5988 was ligated to the PCR-generated PstI, EcoRI restrictionfragment. Restriction analysis was with NcoI, NsiI and EcoRI in a tripledigest. Positive clones contained a 170 base pair NcoI, NsiI restrictionfragment and a 93 base pair NsiI, EcoRI restriction fragment in whichthe bases encoding amino acids 77-82 of hIL-3 have been deleted.pMON6474 was made to serve as the template for the creation of singleamino acid substitution variants at positions 77, 78, 79, 80, 81 and 82of hIL-3.

EXAMPLE 33 Construction of Plasmid pMON6475

Amino acids 83-88 of hIL-3 were deleted using site-directed PCRmutagenesis methods described previously. Plasmid pMON5988 DNA was thetemplate in the reaction using the oligonucleotides, Oligo #26 and Oligo#38, as primers. The resulting PCR-generated DNA product was digestedwith PstI and EcoRI. The PstI, EcoRI restriction fragment from pMON5988was ligated to the PCR-generated PstI, EcoRI restriction fragment.Restriction analysis was with NcoI, NsiI and EcoRI in a triple digest.Positive clones contained a 170 base pair NcoI, NsiI restrictionfragment and a 93 base pair NsiI, EcoRI restriction fragment in whichthe bases encoding amino acids 83-88 of hIL-3 have been deleted.pMON6475 was made to serve as the template for the creation of singleamino acid substitution variants at positions 83, 84, 85, 86, 87 and 88of hIL-3.

EXAMPLE 34 Construction of Plasmid pMON6476

Amino acids 88-93 of hIL-3 were deleted using site-directed PCRmutagenesis methods described previously. Plasmid pMON6458 DNA was thetemplate in the reaction using the oligonucleotides, Oligo #7 and Oligo#39, as primers. The resulting PCR-generated DNA product was purifiedand digested with NcoI and EcoRI. The NcoI, EcoRI restriction fragmentfrom pMON6458 was ligated to the PCR-generated NcoI, EcoRI restrictionfragment. Positive clones contained a 263 base pair NcoI, EcoRIrestriction fragment in which the bases encoding amino acids 88-93 ofhIL-3 have been deleted. pMON6476 was made to serve as the template forthe creation of single amino acid substitution variants at positions 88,89, 90, 91, 92 and 93 of hIL-3.

EXAMPLE 35 Construction of Plasmid pMON6477

Amino acids 106-111 of hIL-3 were deleted using site-directed PCRmutagenesis methods described previously. Plasmid pMON6458 DNA was thetemplate in the reaction using the oligonucleotides, Oligo #7 and Oligo#40, as primers. The resulting PCR-generated DNA fragment was purifiedand digested with NcoI and HindIII. The NcoI, HindIII restrictionfragment from pMON6458 was ligated to the PCR-generated NcoI, HindIIIrestriction fragment. Positive clones contained a 327 base pair NcoI,HindIII restriction fragment in which the bases encoding amino acids106-111 of hIL-3 have been deleted. pMON6477 was made to serve as thetemplate for the creation of single amino acid substitution variants atpositions 106, 107, 108, 109, 110 and 111 of hIL-3.

EXAMPLE 36 Construction of Plasmid pMON6478

Amino acids 112-117 of hIL-3 were deleted using site-directed PCRmutagenesis methods described previously. Plasmid pMON6458 DNA was thetemplate in the reaction using the oligonucleotides, Oligo #7 and Oligo#41, as primers. The resulting PCR-generated DNA product was purifiedand digested with NcoI and HindIII. The 4008 bp NcoI, HindIIIrestriction fragment from pMON6458 was ligated to the PCR-generatedNcoI, HindIII restriction fragment. Positive clones contained a 327 basepair NcoI, HindIII restriction fragment in which the bases encodingamino acids 112-117 of hIL-3 have been deleted. pMON6478 was made toserve as the template for the creation of single amino acid substitutionvariants at positions 112, 113, 114, 115, 116 and 117 of hIL-3.

EXAMPLE 37 Construction of Plasmid pMON6479

Amino acids 118-123 of hIL-3 were deleted using site-directed PCRmutagenesis methods described previously. Plasmid pMON6458 DNA was thetemplate in the reaction using the oligonucleotides, Oligo #7 and Oligo#42, as primers. The resulting PCR-generated DNA product was purifiedand digested with NcoI and HindIII. The NcoI, HindIII restrictionfragment from pMON6458 was ligated to the PCR-generated NcoI, HindIIIrestriction fragment. Positive clones contained a 327 base pair NcoI,HindIII restriction fragment in which the bases encoding amino acids118-123 of hIL-3 have been deleted. pMON6479 was made to serve as thetemplate for the creation of single amino acid substitution variants atpositions 118, 119, 120, 121, 122 and 123 of hIL-3.

EXAMPLE 38 Construction of Single Amino Acid Substitution Libraries atPositions 17, 18, 19, 20, 21 and 22

One of the DNA fragments used to construct the plasmids containingsingle amino acid substitutions at positions 17, 18, 19, 20, 21 and 22of hIL-3 was generated by site-directed mutagenesis employing PCRtechniques described previously. In the PCR reaction the plasmidpMON6464 DNA was the template and the following 32 fold degenerateoligonucleotides, Oligo #43, Oligo #44, Oligo #45, Oligo #46, Oligo #47and Oligo #48 were the primers at the C-terminus. The oligonucleotide,Oligo #26, was used as the primer at the N-terminus. The degenerateoligonucleotides replace the eighteen bases, encoding six amino acids,deleted in pMON6464. The degenerate oligonucleotides have G, A, T or Cin the first and second positions and G or C in the third position of asingle codon at amino acid positions 17, 18, 19, 20, 21 and 22 of hIL-3respectively. These degenerate oligonucleotide primers result inlibraries which theoretically contain 32 different codons encoding all20 amino acid substitutions and one translational stop codon at oneposition. At the other five amino acid positions the native hIL-3 DNAsequence was restored. The resulting PCR-generated DNA product wasdigested with NcoI and EcoRV. Plasmid pMON6464 DNA was digested withrestriction enzymes NcoI and EcoRV resulting in a 4190 base pairfragment which was ligated to the PCR-generated NcoI, EcoRV restrictionfragments. Plasmid DNA was isolated and screened by DNA dot blotdifferential hybridization using the oligonucleotide probe, Oligo #139,which had been labeled with p³². Clones shown to be positive by colonyhybridization were selected, plasmid DNA isolated and DNA sequenced todetermine the amino acid substitution.

EXAMPLE 39 Construction of Single Amino Acid Substitution Libraries atPositions 23, 24, 25, 26, 27 and 28

One of the DNA fragments used to construct the plasmids containingsingle amino acid substitutions at positions 23, 24, 25, 26, 27 and 28of hIL-3 was generated by site-directed mutagenesis employing PCRtechniques described previously. In the PCR reaction the plasmidpMON6465 DNA was the template and the following 32 fold degenerateoligonucleotides, Oligo #49, Oligo #50, Oligo #51, Oligo #52, Oligo #53and Oligo #54 were the primers at the C-terminus. The oligonucleotide,Oligo #26, was used as the primer at the N-terminus. The degenerateoligonucleotides replace the eighteen bases, encoding six amino acids,deleted in pMON6465. The degenerate oligonucleotides have G, A, T or Cin the first and second positions and G or C in the third position of asingle codon at amino acid positions 23, 24, 25, 26, 27 and 28 of hIL-3respectively. These degenerate oligonucleotide primers result inlibraries which theoretically contain 32 different codons encoding all20 amino acid substitutions and one translational stop codon at oneposition. At the other five amino acid positions the native hIL-3 DNAsequence was restored. The resulting PCR-generated DNA products werepurified and digested with restriction enzymes NcoI and EcoRV. PlasmidpMON6465 DNA was digested with restriction enzymes NcoI and EcoRV andthe resulting 4190 base pair fragment was ligated to the PCR-generatedNcoI, EcoRV DNA fragments. Transformant bacteria were screened by DNAdot blot differential hybridization using the oligonucleotide probe,Oligo #140, which had been labeled with p³² Clones shown to be positiveby colony hybridization were selected, plasmid DNA isolated and DNAsequenced to determine the amino acid substitution.

EXAMPLE 40 Construction of Single Amino Acid Substitution Libraries atPositions 29, 30, 31, 32, 33 and 34

One of the DNA fragments used to construct the plasmids containingsingle amino acid substitutions at positions 29, 30, 31, 32, 33 and 34of hIL-3 was generated by site-directed mutagenesis employing PCRtechniques described previously. In the PCR reaction the plasmidpMON6466 DNA was the template and the following 32 fold degenerateoligonucleotides, Oligo #55, Oligo #56, Oligo #57, Oligo #58, Oligo #59and Oligo #60 were the primers at the C-terminus. The oligonucleotideOligo #26 was used as the primer at the N-terminus. The degenerateoligonucleotides replace the eighteen bases, encoding six amino acids,deleted in pMON6466. The degenerate oligonucleotides have G, A, T or Cin the first and second positions and G or C in the third position of asingle codon at amino acid positions 29, 30, 31, 32, 33 and 34 of hIL-3respectively. These degenerate oligonucleotide primers result inlibraries which theoretically contain 32 different codons encoding all20 amino acid substitutions and one translational stop codon at oneposition. At the other five amino acid positions the native hIL-3 DNAsequence was restored. The resulting PCR-generated DNA products werepurified and digested with the restriction enzymes NcoI and EcoRV.Plasmid pMON6466 DNA was digested with restriction enzymes NcoI andEcoRV and the resulting 4190 base pair fragment was ligated to thePCR-generated NcoI, EcoRV DNA fragments. Transformant bacteria werescreened by DNA dot blot differential hybridization using theoligonucleotide probe, Oligo #141, which had been labeled with p³².Clones shown to be positive by colony hybridization were selected,plasmid DNA isolated and DNA sequenced to determine the amino acidsubstitution.

EXAMPLE 41

Construction of single amino acid substitution libraries at positions35, 36, 37, 38, 39 and 40

One of the DNA fragments used to construct the plasmids containingsingle amino acid substitutions at positions 35, 36, 37, 38, 39 and 40of hIL-3 were generated by site-directed mutagenesis employing PCRtechniques described previously. In the PCR reaction the plasmidpMON6467 DNA was the template and the following 32 fold degenerateoligonucleotides, Oligo #61, Oligo #62, Oligo #63, Oligo #64, Oligo #65and Oligo #66 were the primers at the C-terminus. The oligonucleotide,Oligo #7, was used as the primer at the N-terminus. The degenerateoligonucleotides replace the eighteen bases, encoding six amino acids,deleted in pMON6467. The degenerate oligonucleotides have G, A, T or Cin the first and second positions and G or C in the third position of asingle codon at amino acid positions 35, 36, 37, 38, 39 and 40 of hIL-3respectively. These degenerate oligonucleotide primers result inlibraries which theoretically contain 32 different codons encoding all20 amino acid substitutions and one translational stop codon at oneposition. At the other five amino acid positions the native hIL-3 DNAsequence was restored and at the other position, 32 different codonssubstitutions were created at positions independently. The resultingPCR-generated DNA products were purified and digested with therestriction enzymes NcoI and EcoRV. Plasmid pMON6467 DNA was digestedwith restriction enzymes NcoI and EcoRV and the resulting 4190 base pairfragment was ligated to the PCR-generated NcoI, EcoRV DNA fragments.Transformant bacteria were screened by DNA dot blot differentialhybridization using the oligonucleotide probe, Oligo #142, which hadbeen labeled with P³². Clones shown to be positive by colonyhybridization were selected, plasmid DNA isolated and DNA sequenced todetermine the amino acid substitution.

EXAMPLES 42

Construction of single amino acid substitution libraries at positions41, 42, 43, 44, 45 and 46

One of the DNA fragments used to construct the plasmids containingsingle amino acid substitutions at positions 41, 42, 43, 44, 45 and 46of hIL-3 was generated by site-directed mutagenesis employing PCRtechniques described previously. In the PCR reaction the plasmidpMON6468 DNA was the template and the following 32 fold degenerateoligonucleotides, Oligo #67, Oligo #68, Oligo #69, Oligo #70, Oligo #71and Oligo #72 were the primers at the C-terminus. The oligonucleotide,Oligo #7, was used as the primer at the N-terminus. The degenerateoligonucleotides replace the eighteen bases, encoding six amino acids,deleted in pMON6468. The degenerate oligonucleotides have G, A, T or Cin the first and second positions and G or C in the third position of asingle codon at amino acid positions 41, 42, 43, 44, 45 and 46 of hIL-3respectively. These degenerate oligonucleotide primers result inlibraries which theoretically contain 32 different codons encoding all20 amino acid substitutions and one translational stop codon at oneposition. At the other five amino acid positions the native hIL-3 DNAsequence was restored. The resulting PCR-generated DNA products werepurified and digested with the restriction enzymes NcoI and XhoI.Plasmid pMON6468 DNA was digested with restriction enzymes NcoI and XhoIand the resulting 4152 base pair fragment was ligated to thePCR-generated NcoI, XhoI DNA fragments. Transformant bacteria werescreened by DNA dot blot differential hybridization using theoligonucleotide probe, Oligo #143, which had been labeled with P³².Clones shown to be positive by colony hybridization were selected,plasmid DNA isolated and DNA sequenced to determine the amino acidsubstitution.

EXAMPLE 43

Construction of single amino acid substitution libraries at positions47, 48, 49, 50, 51 and 52

One of the DNA fragments used to construct the plasmids containingsingle amino acid substitutions at positions 47, 48, 49, 50, 51 and 52of hIL-3 was generated by site-directed mutagenesis employing PCRtechniques described previously. In the PCR reaction the plasmidpMON6469 DNA was the template and the following 32 fold degenerateoligonucleotides, Oligo #73, Oligo #74, Oligo #75, Oligo #76, Oligo #77and Oligo #78, were the primers at the C-terminus. The oligonucleotide,Oligo #7, was used as the primer at the N-terminus. The degenerateoligonucleotides replace the eighteen bases, encoding six amino acids,deleted in pMON6469. The degenerate oligonucleotides have G, A, T or Cin the first and second positions and G or C in the third position of asingle codon at amino acid positions 47, 48, 49, 50, 51 and 52 of hIL-3respectively. These degenerate oligonucleotide primers result inlibraries which theoretically contain 32 different codons encoding all20 amino acid substitutions and one translational stop codon at oneposition. At the other five amino acid positions the native hIL-3 DNAsequence was restored. The resulting PCR-generated DNA products werepurified and digested with the restriction enzymes NcoI and XhoI.Plasmid pMON6469 DNA was digested with restriction enzymes NcoI and XhoIand the resulting 4152 base pair fragment was ligated to thePCR-generated NcoI, XhoI DNA fragments. Transformant bacteria werescreened by DNA dot blot differential hybridization using theoligonucleotide probe, Oligo #144, which had been labeled with P³².Clones shown to be positive by colony hybridization were selected,plasmid DNA isolated and DNA sequenced to determine the amino acidsubstitution.

EXAMPLE 44

Construction of single amino acid substitution libraries at positions53, 54, 55, 56, 57 and 58

One of the DNA fragments used to construct the plasmids containingsingle amino acid substitutions at positions 53, 54, 55, 56, 57 and 58of hIL-3 was generated by site-directed mutagenesis employing PCRtechniques described previously. In the PCR reaction the plasmidpMON6470 DNA was the template and the following 32 fold degenerateoligonucleotides, Oligo #79, Oligo #80, Oligo #81, Oligo #82, Oligo #83and Oligo #84, were the primers at the C-terminus. The oligonucleotide,Oligo #7, was used as the primer at the N-terminus. The degenerateoligonucleotides replace the eighteen bases, encoding six amino acids,deleted in pMON6470. The degenerate oligonucleotides have G, A, T or Cin the first and second positions and G or C in the third position of asingle codon at amino acid positions 53, 54, 55, 56, 57 and 58 of hIL-3respectively. These degenerate oligonucleotide primers result inlibraries which theoretically contain 32 different codons encoding all20 amino acid substitutions and one translational stop codon at oneposition. At the other five amino acid positions the native hIL-3 DNAsequence was restored. The resulting PCR-generated DNA products werepurified and digested with the restriction enzymes NcoI and NsiI.Plasmid pMON6470 DNA was digested with restriction enzymes NcoI and NsiIand the resulting 4119 base pair fragment was ligated to thePCR-generated NcoI, NsiI DNA fragments. Transformant bacteria werescreened by DNA dot blot differential hybridization using theoligonucleotide probe, Oligo #145, which had been labeled with P³².Clones shown to be positive by colony hybridization were selected,plasmid DNA isolated and DNA sequenced to determine the amino acidsubstitution.

EXAMPLE 45

Construction of single amino acid substitution libraries at positions59, 60, 61, 62, 63 and 64

One of the DNA fragments used to construct the plasmids containingsingle amino acid substitutions at positions 59, 60, 61, 62, 63 and 64of hIL-3 was generated by site-directed mutagenesis employing PCRtechniques described previously. In the PCR reaction the plasmidpMON6471 DNA was the template and the following 32 fold degenerateoligonucleotides, Oligo #85, Oligo #86, Oligo #87, Oligo #88, Oligo #89and Oligo #90, were the primers at the C-terminus. The oligonucleotide,Oligo #7, was used as the primer at the N-terminus. The degenerateoligonucleotides replace the eighteen bases, encoding six amino acids,deleted in pMON6471. The degenerate oligonucleotides have G, A, T or Cin the first and second positions and G or C in the third position of asingle codon at amino acid positions 59, 60, 61, 62, 63 and 64 of hIL-3respectively. These degenerate oligonucleotide primers result inlibraries which theoretically contain 32 different codons encoding all20 amino acid substitutions and one translational stop codon at oneposition. At the other five amino acid positions the native hIL-3 DNAsequence was restored. The resulting PCR-generated DNA products werepurified and digested with the restriction enzymes NcoI and NsiI.Plasmid pMON6471 DNA was digested with restriction enzymes NcoI and NsiIand the resulting 4119 base pair fragment was ligated to thePCR-generated NcoI, Nail DNA fragments. Transformant bacteria werescreened by DNA dot blot differential hybridization using theoligonucleotide probe, Oligo #146, which had been labeled with P³².Clones shown to be positive by colony hybridization were selected,plasmid DNA isolated and DNA sequenced to determine the amino acidsubstitution.

EXAMPLE 46

Construction of single amino acid substitution libraries at positions65, 66, 67, 68, 69 and 70

One of the DNA fragments used to construct the plasmids containingsingle amino acid substitutions at positions 65, 66, 67, 68, 69 and 70of hIL-3 was generated by site-directed mutagenesis employing PCRtechniques described previously. In the PCR reaction the plasmidpMON6472 DNA was the template and the following 32 fold degenerateoligonucleotides, Oligo #91, Oligo #92, Oligo #93, Oligo #94, Oligo #95and Oligo #96, were the primers at the N-terminus. The oligonucleotide,Oligo #26, was used as the primer at the C-terminus. The degenerateoligonucleotides replace the eighteen bases, encoding six amino acids,deleted in pMON6472. The degenerate oligonucleotides have G, A, T or Cin the first and second positions and G or C in the third position of asingle codon at amino acid positions 65, 66, 67, 68, 69 and 70 of hIL-3respectively. These degenerate oligonucleotide primers result inlibraries which theoretically contain 32 different codons encoding all20 amino acid substitutions and one translational stop codon at oneposition. At the other five amino acid positions the native hIL-3 DNAsequence was restored. The resulting PCR-generated DNA products werepurified and digested with the restriction enzymes EcoRI and XhoI.Plasmid pMON6472 DNA was digested with restriction enzymes EcoRI andXhoI and the resulting 4145 base pair fragment was ligated to thePCR-generated EcoRI, XhoI DNA fragments. Transformant bacteria werescreened by DNA dot blot differential hybridization using theoligonucleotide probe, Oligo #147, which had been labeled with P³².Clones shown to be positive by colony hybridization were selected,plasmid DNA isolated and DNA sequenced to determine the amino acidsubstitution.

EXAMPLE 47

Construction of single amino acid substitution libraries at positions71, 72, 73, 74, 75 and 76

One of the DNA fragments used to construct the plasmids containingsingle amino acid substitutions at positions 71, 72, 73, 74, 75 and 76of hIL-3 was generated by site-directed mutagenesis employing PCRtechniques described previously. In the PCR reaction the plasmidpMON6473 DNA was the template and the following 32 fold degenerateoligonucleotides, Oligo #97, Oligo #98, Oligo #99, Oligo #100, Oligo#101 and Oligo #102, were the primers at the N-terminus. Theoligonucleotide, Oligo #26, was used as the primer at the C-terminus.The degenerate oligonucleotides replace the eighteen bases, encoding sixamino acids, deleted in pMON6473. The degenerate oligonucleotides haveG, A, T or C in the first and second positions and G or C in the thirdposition of a single codon at amino acid positions 71, 72, 73, 74, 75and 76 of hIL-3 respectively. These degenerate oligonucleotide primersresult in libraries which theoretically contain 32 different codonsencoding all 20 amino acid substitutions and one translational stopcodon at one position. At the other five amino acid positions the nativehIL-3 DNA sequence was restored. The resulting PCR-generated DNAfragments were purified and digested with the restriction enzymes EcoRIand PstI. Plasmid pMON6473 DNA was digested with restriction enzymesEcoRI and PstI and the resulting 4171 base pair fragment was ligated tothe PCR-generated EcoRI, PstI DNA fragments. Transformant bacteria werescreened by DNA dot blot differential hybridization using theoligonucleotide probe, Oligo #148, which had been labeled with P³².Clones shown to be positive by colony hybridization were selected,plasmid DNA isolated and DNA sequenced to determine the amino acidsubstitution.

EXAMPLE 48

Construction of single amino acid substitution libraries at positions77, 78, 79, 80, 81 and 82

One of the DNA fragments used to construct the plasmids containingsingle amino acid substitutions at positions 77, 78, 79, 80, 81 and 82of hIL-3 was generated by site-directed mutagenesis employing PCRtechniques described previously. In the reaction the plasmid pMON6474DNA was the template and the following 32 fold degenerateoligonucleotides, Oligo #103, Oligo #104, Oligo #105, Oligo #106, Oligo#107 and Oligo #108, were the primers at the N-terminus. Theoligonucleotide, Oligo #26, was used as the primer at the C-terminus.The degenerate oligonucleotides replace the eighteen bases, encoding sixamino acids, deleted in pMON6474. The degenerate oligonucleotides haveG, A, T or C in the first and second positions and G or C in the thirdposition of a single codon at amino acid positions 77, 78, 79, 80, 81and 82 of hIL-3 respectively. These degenerate oligonucleotide primersresult in libraries which theoretically contain 32 different codonsencoding all 20 amino acid substitutions and one translational stopcodon at one position. At the other five amino acid positions the nativehIL-3 DNA sequence was restored. The resulting PCR-generated DNAproducts were purified and digested with the restriction enzymes EcoRIand PstI as described previosly. Plasmid pMON6474 DNA was digested withrestriction enzymes EcoRI and PstI and the resulting 4171 base pairfragment was ligated to the PCR-generated EcoRI, PstI DNA fragments.Transformant bacteria were screened by DNA dot blot differentialhybridization using the oligonucleotide probe, Oligo #149, which hadbeen labeled with P³². Clones shown to be positive by colonyhybridization were selected, plasmid DNA isolated and DNA sequenced todetermine the amino acid substitution.

EXAMPLE 49

Construction of single amino acid substitution libraries at positions83, 84, 85, 86, 87 and 88

One of the DNA fragments used to construct the plasmids containingsingle amino acid substitutions at positions 83, 84, 85, 86, 87 and 88of hIL-3 was generated by site-directed mutagenesis employing PCRtechniques described previously. In the PCR reaction the plasmidpMON6475 DNA was the template and the following 32 fold degenerateoligonucleotides, Oligo #109, Oligo #110, Oligo #111, Oligo #112, Oligo#113 and Oligo #114, were the primers at the N-terminus. Theoligonucleotide, Oligo #26, was used as the primer at the C-terminus.The degenerate oligonucleotides replace the eighteen bases, encoding sixamino acids, deleted in pMON6475. The degenerate oligonucleotides haveG, A, T or C in the first and second positions and G or C in the thirdposition of a single codon at amino acid positions 83, 84, 85, 86, 87and 88 of hIL-3 respectively. These degenerate oligonucleotide primersresult in libraries which theoretically contain 32 different codonsencoding all 20 amino acid substitutions and one translational stopcodon at one position. At the other five amino acid positions the nativehIL-3 DNA sequence was restored. The resulting PCR-generated DNA producswere purified and digested with the restriction enzymes EcoRI and PstI.Plasmid pMON6475 DNA was digested with restriction enzymes EcoRI andPstI and the resulting 4171 base pair fragment was ligated to thePCR-generated EcoRI, PstI DNA fragments. Transformant bacteria werescreened by DNA dot blot differential hybridization using theoligonucleotide probe, Oligo #150, which had been labeled with P³².Clones shown to be positive by colony hybridization were selected,plasmid DNA isolated and DNA sequenced to determine the amino acidsubstitution.

EXAMPLE 50

Construction of single amino acid substitution libraries at positions88, 89, 90, 91, 92 and 93

One of the DNA fragments used to construct the plasmids containingsingle amino acid substitutions at positions 88, 89, 90, 91, 92 and 93of hIL-3 was generated by site-directed mutagenesis employing PCRtechniques described previously. In the PCR reaction the plasmidpMON6476 DNA was the template and the following degenerateoligonucleotides, Oligo #114, Oligo #115, Oligo #116, Oligo #117, Oligo#118 and Oligo #119, were the primers at the C-terminus. Theoligonucleotide, Oligo #7, was used as the primer at the N-terminus. Thedegenerate oligonucleotides replace the eighteen bases, encoding sixamino acids, deleted in pMON6476. The degenerate oligonucleotides haveG, A, T or C in the first and second positions and G or C in the thirdposition of a single codon at amino acid positions 88, 89, 90, 91, 92and 93 of hIL-3 respectively. These degenerate oligonucleotide primersresult in libraries which theoretically contain 32 different codonsencoding all 20 amino acid substitutions and one translational stopcodon at one position. At the other five amino acid positions the nativehIL-3 DNA sequence was restored. The resulting PCR-generated DNAproducts were purified and digested with the restriction enzymes EcoRIand NcoI. Plasmid pMON6476 DNA was digested with restriction enzymesEcoRI and NcoI and the resulting 4008 base pair fragment was ligated tothe PCR-generated EcoRI, NcoI DNA fragments. Transformant bacteria werescreened by DNA dot blot differential hybridization using theoligonucleotide probe, Oligo #151, which had been labeled with P³².Clones shown to be positive by colony hybridization were selected,plasmid DNA isolated and DNA sequenced to determine the amino acidsubstitution.

EXAMPLE 51

Construction of single amino acid substitution libraries at positions106, 107, 108, 109, 110 and 111

One of the DNA fragments used to construct the plasmids containing thesingle amino acid substitutions at positions 106, 107, 108, 109, 110 and111 of hIL-3 was generated by site-directed mutagenesis employing PCRtechniques described previously in two sequential PCR reactions. In thefirst PCR reaction, plasmid pMON6477 DNA was the template and thefollowing 32 fold degenerate oligonucleotides, Oligo #120, Oligo #121,Oligo #122, Oligo #123, Oligo #124 and Oligo #125 were the primers atthe C-terminus. The oligonucleotide, Oligo #7 was the primer at theN-terminus. The degenerate oligonucleotides replace the eighteen bases,encoding six amino acids, deleted in pMON6477. The degenerateoligonucleotides have G, A, T or C in the first and second positions andG or C in the third position of a single codon at amino acid positions106, 107, 108, 109, 110 and 111 of hIL-3 respectively. These degenerateoligonucleotide primers result in libraries which theoretically contain32 different codons encoding all 20 amino acid substitutions and onetranslational stop codon at one position. At the other five amino acidpositions the native hIL-3 DNA sequence was restored. The DNA generatedin this PCR reaction was purified by phenol/chloroform extraction andprecipitation with equal volume isopropanol in the presence of 2M NH₄OAc to remove any primer that was not extended. This DNA was then usedas a primer in the second PCR reaction.

In the second PCR reaction plasmid pMON6477 DNA was the template, theDNA product generated in the first PCR reaction (described above) wasthe primer at the N-terminus and the oligonucleotide, Oligo #126 (DNAsequence shown in Table 1), was the primer at the C-terminus. Theresulting PCR-generated DNA products were purified and digested with therestriction enzymes HindIII and NcoI. Plasmid pMON6477 was digested withrestriction enzymes HindIII and NcoI and the resulting 3944 base pairfragment was ligated to the PCR-generated HindIII, NcoI DNA fragments.Transformant bacteria were screened by DNA dot blot differentialhybridization using the oligonucleotide probe, Oligo #152, which hadbeen labeled with P³². Clones shown to be positive by colonyhybridization were selected, plasmid DNA isolated and DNA sequenced todetermine the amino acid substitution.

EXAMPLE 52

Construction of single amino acid substitution libraries at positions112, 113, 114, 115, 116 and 117

One of the DNA fragments used to construct the plasmids containingsingle amino acid substitutions at positions 112, 113, 114, 115, 116 and117 of hIL-3 was generated by site-directed mutagenesis employing PCRtechniques described previously. In the PCR reaction the plasmidpMON6478 DNA was the template and the following 32 fold degenerateoligonucleotides, Oligo #127, Oligo #128, Oligo #129, Oligo #130, Oligo#131 and Oligo #132, were the primers at the C-terminus. Theoligonucleotide, Oligo #7, was used as the primer at the N-terminus. Thedegenerate oligonucleotides replace the eighteen bases, encoding sixamino acids, deleted in pMON6478. The degenerate oligonucleotides haveG, A, T or C in the first and second positions and G or C in the thirdposition of a single codon at amino acid positions 112, 113, 114, 115,116 and 117 of hIL-3 respectively. These degenerate oligonucleotideprimers result in libraries which theoretically contain 32 differentcodons encoding all 20 amino acid substitutions and one translationalstop codon at one position. At the other five amino acid positions thenative hIL-3 DNA sequence was restored. The resulting PCR-generated DNAproducts were purified and digested with the restriction enzymes HindIIIand NcoI. Plasmid pMON6478 was digested with restriction enzymes HindIIIand NcoI and the resulting 3944 base pair fragment was ligated to thePCR-generated HindIII, NcoI DNA fragments. Transformant bacteria werescreened by DNA dot blot differential hybridization using theoligonucleotide probe, Oligo #153, which had been labeled with P³².Clones shown to be positive by colony hybridization were selected,plasmid DNA isolated and DNA sequenced to determine the amino acidsubstitution.

EXAMPLE 53

Construction of single amino acid substitution libraries at positions118, 119, 120, 121, 122 and 123

One of the DNA fragments used to construct the plasmids containingsingle amino acid substitutions at positions 118, 119, 120, 121, 122 and123 of hIL-3 was generated by site-directed mutagenesis employing PCRtechniques described previously. In the PCR reaction the plasmidpMON6479 DNA was the template and the following 32 fold degenerateoligonucleotides, Oligo #133, Oligo #134, Oligo #135, Oligo #136, Oligo#137 and Oligo #138, were the primers at the C-terminus. Theoligonucleotide, Oligo #7, was used as the primer at the N-terminus. Thedegenerate oligonucleotides replace the eighteen bases, encoding sixamino acids, deleted in pMON6479. The degenerate oligonucleotides haveG, A, T or C in the first and second positions and G or C in the thirdposition of a single codon at amino acid positions 118, 119, 120, 121,122 and 123 of hIL-3 respectively. These degenerate oligonucleotideprimers result in libraries which theoretically contain 32 differentcodons encoding all 20 amino acid substitutions and one translationalstop codon at one position. At the other five amino acid positions thenative hIL-3 DNA sequence was restored. The resulting PCR-generated DNAproducts were purified and digested with the restriction enzymes HindIIIand NcoI. Plasmid pMON6479 DNA was digested with restriction enzymesHindIII and NcoI and the resulting 3944 base pair fragment was ligatedto the PCR-generated HindIII, NcoI DNA fragments. Transformant bacteriawere screened by DNA dot blot differential hybridization using theoligonucleotide probe, Oligo #154, which had been labeled with P³².Clones shown to be positive by colony hybridization were selected,plasmid DNA isolated and DNA sequenced to determine the amino acidsubstitution.

EXAMPLE 54

Construction of pMON13358

Plasmid pMON5978 DNA (Example 6) was digested with restriction enzymesNsiI and EcoRI and the resulting 3853 base pair NsiI, EcoRI fragmentcontains the following genetic elements; beta-lactamase gene (AMP),pBR327 origin of replication, phage f1 origin of replication as thetranscription terminator, recA promoter, g10L ribosome binding site andthe bases encoding amino acids 15-71 and 106-125 of (15-125) hIL-3. The3853 base pair NsiI, EcoRI restriction fragment from pMON5978 wasligated to the following annealed complementary oligonucleotides.

Oligo #15(A) [SEQ ID NO: 29]

Oligo #16(A) [SEQ ID NO: 30]

In the resulting plasmid the 111 bases between the NsiI and EcoRIrestriction sites in the (15-125) hIL-3 gene are replaced with 24 basesfrom the above mentioned oligonucleotides. This linker also creates aNdeI recognition sequence.

EXAMPLE 55

Construction of pMON13304

Plasmid pMON13358 DNA is digested with restriction enzymes PstI andEcoRI and the resulting 3846 base pair PstI, EcoRI fragment contains thefollowing genetic elements; beta-lactamase gene (AMP), pBR327 origin ofreplication, phage f1 origin of replication as the transcriptionterminator, recA promoter, g10L ribosome binding site and the basesencoding amino acids 15-69 and 106-125 of (15-125) hIL-3. The 3846 basepair NsiI ,EcoRI restriction fragment from pMON13358 is ligated to thefollowing annealed complementary oligonucleotides.

Oligo #155 [SEQ ID NO:200]

Oligo #156 [SEQ ID NO:201]

Oligo #157 [SEQ ID NO:202]

Oligo #158 [SEQ ID NO:203]

Oligo #159 [SEQ ID NO:204]

Oligo #160 [SEQ ID NO:205]

Oligo #161 [SEQ ID NO:206]

Oligo #162 [SEQ ID NO:207]

When assembled, the oligonucleotides create PstI and EcoRI restrictionends and the DNA sequence that encodes amino acids 70-105 of (15-125)hIL-3 with the following amino acid substitutions; 98I and 100R. Thecodons encoding amino acids 70-105 of (15-125) hIL-3 are those found inthe hIL-3 cDNA sequence except at those positions where amino acidsubstitutions were made. The plasmid, pMON13304, encodes the (15-125)hIL-3 variant with the following amino acid sequence:

Peptide #A1 [SEQ ID NO:66]

EXAMPLE 56

Construction of pMON13305

Plasmid pMON13358 DNA is digested with restriction enzymes PstI andEcoRI and the resulting 3846 base pair PstI, EcoRI fragment contains thefollowing genetic elements; beta-lactamase gene (AMP), pBR327 origin ofreplication, phage f1 origin of replication as the transcriptionterminator, recA promoter, g10L ribosome binding site and the basesencoding amino acids 15-69 and 106-125 of (15-125) hIL-3. The 3846 basepair NsiI , EcoRI restriction fragment from pMON13358 is ligated to thefollowing annealed complementary oligonucleotides.

Oligo #155 [SEQ ID NO:200]

Oligo #156 [SEQ ID NO:201]

Oligo #157 [SEQ ID NO:202]

Oligo #158 [SEQ ID NO:203]

Oligo #159 [SEQ ID NO:204]

Oligo #160 [SEQ ID NO:205]

Oligo #163 [SEQ ID NO:208]

Oligo #164 [SEQ ID NO:209]

When assembled, the oligonucleotides create PstI and EcoRI restrictionends and the DNA sequence that encodes amino acids 70-105 of (15-125)hIL-3 with the following amino acid substitutions; 95R, 98I and 100R.The codons encoding amino acids 70-105 of (15-125) hIL-3 are those foundin the hIL-3 cDNA sequence except at those positions where amino acidsubstitutions were made. The plasmid, pMON13305, encodes the (15-125)hIL-3 variant with the following amino acid sequence:

Peptide #A2 [SEQ ID NO:67]

EXAMPLE 57

Construction of pMON13286

Plasmid pMON5978 DNA was digested with restriction enzymes NcoI andEcoRV and the resulting 3865 base pair NcoI, EcoRV fragment contains thefollowing genetic elements; beta-lactamase gene (AMP), pBR327 origin ofreplication, phage f1 origin of replication as the transcriptionterminator, precA promoter, g10L ribosome binding site and the basesencoding amino acids 47-125 of (15-125) hIL-3. The 3865 base pair NcoI,EcoRV restriction fragment from pMON5978 was ligated to the followingannealed complementary oligonucleotides.

Oligo #165 [SEQ ID NO:210]

Oligo #166 [SEQ ID NO:211]

Oligo #167 [SEQ ID NO:212]

Oligo #168 [SEQ ID NO:213]

Oligo #169 [SEQ ID NO:214]

Oligo #170 [SEQ ID NO:215]

When assembled, the oligonucleotides create NcoI and EcoRV restrictionends and the DNA sequence that encodes amino acids 15-46 of (15-125)hIL-3 with the following amino acid substitutions; 42D, 45M and 46S. Thecodons encoding amino acids 15-46 of (15-125) hIL-3 are those found inthe hIL-3 cDNA sequence except at those positions where amino acidsubstitutions were made. The plasmid, pMON13286, encodes the (15-125)hIL-3 variant with the following amino acid sequence:

    Peptide #A3 [SEQ ID NO:69]                                                       - DNA sequence #A4 pMON13286 42D, 45M, 46S                                    - ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA [SEQ ID NO:                                                  68]                                   - GCCACCGCTG CCGCTGCTGG ACTTCAACAA CCTCAATGAC GAAGACATGT                      - CTATCCTGAT GGAAAATAAC CTTCGTCGTC CAAACCTCGA GGCATTCAAC                      - CGTGCTGTCA AGTCTCTGCA GAATGCATCA GCAATTGAGA GCATTCTTAA                      - AAATCTCCTG CCATGTCTGC CCCTGGCCAC GGCCGCACCC ACGCGACATC                      - CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC                      - TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAG                           

EXAMPLE 58

Construction of pMON5853 (FIG. 6) which encodes [Met-(15-133) hIL-3(Arg¹²⁹)]P Plasmid DNA of pMON5847 (Example 2) was treated with NcoI.The restriction enzyme was inactivated by heat treatment (65° C. for 10minutes). The DNA was then treated with large fragment of DNA polymeraseI (Klenow) in the presence of all four nucleotide precursors. Thisproduces DNA termini with non-overlapping ends. After 5 minutes at 37°C., the polymerase was inactivated by heat treatment at 65° C. for 10minutes. The DNA was then treated with HpaI, an enzyme which producesnon-overlapping termini. The DNA was ethanol precipitated and ligated.The ligation reaction mixture was used to transform competent JM101cells to ampicillin resistance. Colonies were picked and plasmid DNA wasanalyzed by restriction analysis. A plasmid designated pMON5853 wasidentified as one containing a deletion of the amino terminal 14 codonsof the hIL-3 gene. The DNA sequence for the junction of the ribosomebinding site to the (15-133) hIL-3 gene was determined to be thefollowing:

    5'-AAGGAGATATATCCATGAACTGCTCTAAC-3'                                                                  [SEQ ID NO:133]                                                           M  N  C  S  N [SEQ ID NO:134]                          

The lower line contains the one-letter code for the amino acidsspecified by the coding sequence of the amino terminus of the 15-133hIL-3 gene. These are methionine, asparagine, cysteine, serine andasparagine.

When cultures of JM101 cells harboring this plasmid were induced withnalidixic acid, it was found that hIL-3 (15-133) accumulated at levelshigher than hIL-3 (pMON5847).

The plasmid, pMON5853, encodes Met-(15-133) hIL-3 (Arg¹²⁹) which has thefollowing amino acid sequence:

                         [SEQ ID NO:135]                                             -                                                                              Met Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr                              - His Leu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn                         - Asn Leu Asn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn                         - Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg Ala                         - Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile                         - Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala                         - Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp                         - Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys                         - Thr Leu Glu Asn Ala Gln Ala Gln Gln Thr Thr Leu Arg                         - Leu Ala Ile Phe                                                      

Formula XI shown below is a representation of a [(15-125) hIL-3 mutein]with numbers in bold type added above the amino acids to represent theposition at which the amino acid below the bolded number appears innative (1-133) hIL-3 [e. g. the amino acid at position 1 of Formula XIcorresponds to the Asn which appears at position 15 in native (1-133)hIL-3]. The number shown in bold indicates the amino acids thatcorrespond to the native IL-3(1-133). The non-bold members below theamino acids sequences are for Seq Id reference numbers. When the muteinsare expressed the initial amino acid may be preceded by Met- orMet-Ala-.

     15                  20                  25                                     Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln [SEQ ID                                                      NO:23]                              1                5                  10                  15                    -  30                  35                  40                                Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp                                    20                  25                  30                    -  45                  50                  55                                Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu                                    35                  40                  45                    -  60                  65                  70                                Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile                                    50                  55                  60                    -  75                  80                  85                                Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr                                    65                  70                  75                    -  90                  95                 100                                Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp                                    80                  85                  90                    - 105                 110                 115                                Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu                                    95                 100                 105                    - 120                 125                                                    Asn Ala Gln Ala Gln Gln                                                                       110                                                     

Table 6 shows (15-125) hIL-3 muteins of the present invention which haveone (and in some cases two) amino acid substitutions in the (15-125)hIL-3 polypeptide and which were constructed as described in theExamples. The mutants in Table 6 were secreted into the periplasmicspace in E. coli. The periplasmic content was released by osmotic shockand the material in the crude osmotic shock fraction was screened forgrowth promoting activity. Biological activity is the growth promotingactivity of AML cells relative to (15-125) hIL-3 (pMON6458 orpMMON5988). The numbers in parentheses indicate the number of repeatassays. When a variant was assayed more than once the standard deviationis indicated. An "-" indicates that the hIL3 variant protein level wasless than 1.0 μg/ml and was not screened for growth promoting activity.

                  TABLE 6                                                         ______________________________________                                        (15-125) HUMAN INTERLEUKIN-3 MUTANTS                                            hIL-3           (15-125)hIL-3 MUTANT                                        aa    PARENTAL            SEQ                                                 POSI-        CO-            ID   CO-                                            TION.sup.1 aa DON aa NO: DON BIOL ACTIVITY                                  ______________________________________                                        17/3.sup.1                                                                          SER    TCT      LYS   19   AAG  <0.018 (1)                                17/3 SER TCT GLY 19 GGG 1.2 ± 1.1 (3)                                      17/3 SER TCT ASP 19 GAC 1.0 ± 0.7 (3)                                      17/3 SER TCT MET 19 ATG 0.50 (1)                                              17/3 SER TCT GLN 19 CAG 1.2 ± 0.7 (3)                                      17/3 SER TCT ARG 19 AGG <0.070 (1)                                            16/4 ASN AAC HIS 19 CAC 1.2 ± 0.3 (3)                                      18/4 ASN AAC LEU 19 CTC 0.45 ± 0.42 (4)                                    18/4 ASN AAC ILE 19 ATC 1.5 ± 0.2 (2)                                      18/4 ASN AAC PHE 19 TTC 0.19 ± 0.26 (2)                                    18/4 ASN AAC ARG 19 CGC 0.10 (1)                                              18/4 ASN AAC GLN 19 CAA 0.37 (1)                                              19/5 MET ATG PHE 19 TTC 0.25 (1)                                              19/5 MET ATG ILE 19 ATC 0.77 ± 0.70 (9)                                    19/5 MET ATG ARG 19 AGG 0.17 (1)                                              19/5 MET ATC GLY 19 GGA 0.06 (1)                                              19/5 MET ATC ALA 19 GCG 0.19 (1)                                              19/5 MET ATG CYS 19 TGC --                                                    20/6 ILE ATC CYS 19 TGC --                                                    20/6 ILE ATC GLN 19 CAG --                                                    20/6 ILE ATC GLU 19 GAG <0.025 (1)                                            20/6 ILE ATC ARG 19 CGC <0.025 (1)                                            20/6 ILE ATC PRO 19 CCG 0.29 ± 0.16 (3)                                    20/6 ILE ATC ALA 19 GCG 0.18 (1)                                              21/7 ASP GAT PHE 19 TTC <0.016 (1)                                            21/7 ASP GAT LYS 19 AAG 0.027 ± 0.027 (2)                                  21/7 ASP GAT ARG 19 AGG <0.008 (1)                                            21/7 ASP GAT ALA 19 GCG 0.07 ± 0.06 (3)                                    21/7 ASP GAT GLY 19 GGG 0.032 (1)                                             21/7 ASP GAT VAL 19 GTC <0.008 (1)                                            22/8 GLU GAA TRP 19 TGG --                                                    22/8 GLU GAA PRO 19 CCG <0.015 (1)                                            22/8 GLU GAA SER 19 TCG <0.015 (1)                                            22/8 GLU GAA ALA 19 GCC <0.015 (1)                                            22/8 GLU GAA HIS 19 CAC <0.015 (1)                                            22/8 GLU GAA GLY 19 GGC <0.008 (1)                                            23/9 ILE ATT VAL 19 GTG 0.18 (1)                                              23/9 ILE ATT ALA.sup.2 19 GCG 1.16 ± 0.16 (3)                              23/9 ILE ATT LEU 19 TTG 1.3 (1)                                               23/9 ILE ATT GLY.sup.2 19 GGG 0.06 (1)                                        23/9 ILE ATT TRP 19 TCC --                                                    23/9 ILE ATT LYS.sup.3 19 AAC --                                              23/9 ILE ATT PHE 19 TTC --                                                    23/9 ILE ATT LEU.sup.2 19 TTC 3.0 ± 1.1 (3)                                23/9 ILE ATT SER.sup.2 19 AGC <0.005 (1)                                      23/9 ILE ATT ARG.sup.2 19 CGC --                                              24/10 ILE ATA GLY 19 GGG <0.004 (1)                                           24/10 ILE ATA VAL 19 GTC 0.89 ± 0.23 (4)                                   24/10 ILE ATA ARG.sup.3 19 CGG --                                             24/10 ILE ATA SER 19 AGC <0.003 (1)                                           24/10 ILE ATA PHE 19 TTC 0.29 ± 0.24 (2)                                   24/10 ILE ATA LEU 19 CTG 0.52 ± 0.12 (3)                                   25/11 THR ACA HIS 19 CAC 1.11 ± 0.2 (3)                                    25/11 THR ACA GLY 19 GGC 0.48 ± 0.27 (4)                                   25/11 THR ACA GLN 19 CAG 1.0 ± 0.8 (4)                                     25/11 THR ACA ARG 19 CGG 0.26 ± 0.17 (2)                                   25/11 THR ACA PRO 19 CCG 0.36 (1)                                             31/17 PRO CCT GLY 19 GGG 0.79 ± 0.61 (2)                                   31/17 PRO CCT ALA 19 GCC 0.49 (1)                                             31/17 PRO CCT ARG 19 CGC 0.25 ± 0.20 (2)                                   31/17 PRO CCT LEU 19 CTG 0.22 (1)                                             31/17 PRO CCT GLN 19 CAG 0.62 ± 0.04 (2)                                   31/17 PRO CCT LEU.sup.4 19 CTG 0.30 ± 0.20 (3)                             32/18 LEU TTG VAL 19 GTG 0.01 (1)                                             32/18 LEU TTG ARG 19 CGC 1.5 ± 1.0 (4)                                     32/18 LEU TTG GLN 19 CAG 0.93 ± 0.18 (3)                                   32/18 LEU TTG ASN 19 AAC 1.2 ± 0.5 (5)                                     32/18 LEU TTG GLY.sup.5 19 GGC 0.84 ± 1.0 (3)                              32/18 LEU TTG ALA 19 GCG 1.4 ± 0.7 (5)                                     32/18 LEU TTG GLU 19 GAG 0.88 ± 0.37 (2)                                   33/19 PRO CC(T/C) LEU 19 CTG 0.13 (1)                                         33/19 PRO CC(T/C) GLN 19 CAG 0.22 ± 0.20 (2)                               33/19 PRO CC(T/C) ALA 19 GCG 0.30 ± 0.14 (2)                               33/19 PRO CC(T/C) THR 19 ACC <0.018 (1)                                       33/19 PRO CC(T/C) GLU 19 GAG 0.54 ± 0.43 (2)                               34/20 LEU TTG VAL 19 GTG 1.2 ± 0.6 (3)                                     34/20 LEU TTG GLY 19 GGG 0.64 ± 0.74 (2)                                   34/20 LEU TTG SER 19 TCG 1.5 ± 0.7 (4)                                     34/20 LEU TTG LYS 19 AAG 0.97 ± 0.28 (2)                                   34/20 LEU TTG MET 19 ATG 1.7 ± 0.5 (3)                                     35/21 LEU CTG ALA 19 GCC 1.6 ± 0.5 (3)                                     35/21 LEU CTG GLY 19 GGC <0.006 ± 0.002 (3)                                35/21 LEU CTG ASN 19 AAC 1.1 ± 1.7 (5)                                     35/21 LEU CTG PRO 19 CCC 1.8 ± 2.0 (5)                                     35/21 LEU CTG GLN 19 CAA 0.98 ± 1.1 (5)                                    35/21 LEU CTG VAL 19 GTG 0.76 ± 0.86 (5)                                   36/22 ASP GAC LEU 19 CTC 0.20 (1)                                             25/11 THR ACA ALA 19 GCC 0.86 ± 0.27 (3)                                   26/12 HIS CAC THR 19 ACG 0.010 (1)                                            26/12 HIS CAC PHE 19 TTC 0.26 (1)                                             26/12 HIS CAC GLY 19 GGG 0.19 (1)                                             26/12 HIS CAC ARG 19 CGG 0.21 (1)                                             26/12 HIS CAC ALA 19 GCC 0.56 ± 0.03 (2)                                   26/12 HIS CAC TRP 19 TGG --                                                   27/13 LEU TTA GLY 19 GGG --                                                   27/13 LEU TTA ARG 19 AGG --                                                   27/13 LEU TTA THR 19 ATC 0.084 (1)                                            27/13 LEU TTA SER 19 TCC --                                                   27/13 LEU TTA ALA 19 GCG 0.01 (1)                                             28/14 LYS AAG ARG 19 CGG 0.42 ± 0.07 (2)                                   28/14 LYS AAG LEU 19 TTG --                                                   28/14 LYS AAG TRP 19 TGG --                                                   28/14 LYS AAG GLN 19 CAG 0.27 (1)                                             28/14 LYS AAG GLY 19 GGC 0.36 ± 0.07 (2)                                   28/14 LYS AAG PRO 19 CCC 0.10 ± 0.04 (2)                                   28/14 LYS AAG VAL 19 GTG 0.19 ± 0.12 (2)                                   29/15 GLN CAG ASN 19 AAC 1.62 ± 1.7 (3)                                    29/15 GLN CAG LEU 19 CTG 0.284                                                29/15 GLN CAG PRO 19 CCG --                                                   29/15 ARG CAG ARG 19 AGG 0.44 ± 0.16 (4)                                   29/15 GLN CAG VAL 19 GTG 0.62 ± 0.40 (4)                                   30/16 PRO CCA HIS 19 CAC 0.26 (1)                                             30/16 PRO CCA THR 19 ACG 0.36 (1)                                             30/16 PRO CCA GLY 19 GGG 1.2 ± 0.8 (3)                                     30/16 PRO CCA ASP 19 GAC --                                                   30/16 PRO CCA GLN 19 CAG 0.61 ± 0.37 (3)                                   30/16 PRO CCA SER 19 TCG --                                                   30/16 PRO CCA LEU 19 TTC --                                                   30/16 PRO CCA LYS 19 AAG --                                                   31/17 PRO CCT ASP 19 GAC 0.66 ± 0.71 (3)                                   36/22 ASP CAC VAL 19 GTG --                                                   37/23 PHE TTC SER 19 AGC 0.62 ± 0.40 (4)                                   37/23 PHE TTC PRO 19 CCG 0.65 ± 0.39 (4)                                   37/23 PHE TTC TRP 19 TGG --                                                   37/23 PHE TTC ILE 19 ATC 0.1 (1)                                              38/24 ASN AAC ALA 19 GCN 1.9 (1)                                              40/26 LEU CTC TRP 19 TCC --                                                   40/26 LEU CTC ARC 19 CCC --                                                   41/27 ASN AAT CYS 19 TCC 0.18 (1)                                             41/27 ASN AAT ARC 19 CCC 0.13 ± 0.13 (2)                                   41/27 ASN AAT LEU 19 CTC 0.09 ± 0.07 (2)                                   41/27 ASN AAT HIS 19 CAC 0.49 ± 0.26 (4)                                   41/27 ASN AAT MET 19 ATC 0.30 ± 0.38 (4)                                   41/27 ASN AAT PRO 19 CCC 0.12 (1)                                             42/28 GLY GGC ASP 19 GAC 5.7 ± 5.7 (6)                                     42/28 GLY GGG SER 19 ACC 4.3 ± 4.8 (7)                                     42/28 GLY CGC CYS 19 TGC 0.53 (1)                                             42/28 GLY GGC ALA 19 GCC 5.9 ± 4.1 (7)                                     43/29 GLU CAA ASN 19 AAC 0.050 (1)                                            43/29 GLU CAA TYR 19 TAC 0.010 (1)                                            43/29 GLU GAA LEU 19 CTC <0.009 (1)                                           43/29 GLU CAA PHE 19 TTC <0.009 (1)                                           43/29 GLU CAA ASP 19 GAC 0.044 (1)                                            43/29 GLU GAA ALA 19 GCC <0.009 (1)                                           43/29 GLU GAA CYS 19 TG <0.009 (1)                                            43/29 GLU CAA SER 19 AGC <0.009 (1)                                           44/30 ASP GAC SER 19 TCA 0.007 (1)                                            44/30 ASP GAC LEU 19 CTG <0.007 (1)                                           44/30 ASP GAC ARG 19 AGG <0.007 (1)                                           44/30 ASP GAC LYS 19 AAG <0.007 (1)                                           44/30 ASP GAC THR 19 ACG --                                                   44/30 ASP GAC MET 19 ATG <0.007 (1)                                           44/30 ASP GAC TRP 19 TGG <0.007 (1)                                           44/30 ASP GAC PRO 19 CCC <0.007 (1)                                           45/31 GLN CAA PRO 19 CCC --                                                   45/31 GLN CAA PHE 19 TTC 0.007 (1)                                            45/31 GLN CAA VAL 19 GTC 6.7 ± 6.1 (5)                                     45/31 GLN CAA MET 19 ATG 3.4 ± 1.8 (5)                                     45/31 GLN CAA LEU 19 TTG 1.1 ± 1.3 (2)                                     45/31 GLN CAA THR 19 ACG 0.96 ± 1.5 (3)                                    45/31 GLN CAA LYS 19 AAG 1.6 ± 2.2 (5)                                     45/31 GLN CAA TRP 19 TGG 0.10 (1)                                             46/32 ASP GAC PHE 19 TTC 1.2 ± 0.5 (3)                                     46/32 ASP GAC SER 19 TCC 7.9 ± 6.4 (4)                                     46/32 ASP GAC THR 19 ACC 1.8 ± 0.2 (2)                                     46/32 ASP GAC CYS 19 TGC 0.80 (1)                                             46/32 ASP GAC GLY 19 GGC 0.25 (1)                                             47/33 ILE ATT GLY 19 GGC <0.015 (1)                                           47/33 ILE ATT VAL 19 GTG 0.38 (1)                                             47/33 ILE ATT HIS 19 CAC 0.10 (1)                                             47/33 ILE ATT SER 19 TCC 0.03 (1)                                             47/33 ILE ATT ARC 19 AGG 0.09 (1)                                             47/33 ILE ATT PRO 19 CCG <0.015 (1)                                           48/34 LEU CTG SER 19 AGC <0.009 (1)                                           48/34 LEU CTG CYS 19 TCG --                                                   48/34 LEU CTG ARG 19 CGC <0.009 (1)                                           48/34 LEU CTG ILE 19 ATC 0.036 (1)                                            48/34 LEU CTC HIS 19 CAC <0.009 (1)                                           48/34 LEU CTG PHE 19 TTC <0.009 (1)                                           48/34 LEU CTG ASN 19 AAC <0.009 (1)                                           49/35 MET ATG ARG 19 CGC 0.007 (1)                                            49/35 MET ATG ALA 19 GCC 0.091 (1)                                            49/35 MET ATG GLY 19 GGC 0.036 (1)                                            49/35 MET ATG PRO 19 CCC <0.009 (1)                                           49/35 MET ATG ASN 19 AAC 0.23 (1)                                             49/35 MET ATG HIS 19 CAC <0.009 (1)                                           49/35 MET ATG ASP 19 GAC 0.28 ± 0.48 (3)                                   50/36 GLU GAA LEU 19 CTC 0.01 (1)                                             50/36 GLU GAA THR 19 ACC 0.20 (1)                                             50/36 GLU GAA ASP 19 GAC --                                                   50/36 GLU GAA TYR 19 TAC 0.09 (1)                                             50/36 GLU GAA GLN 19 CTG 0.02 (1)                                             51/37 ASN AAT ARG 19 CGC 2.0 ± 0.8 (3)                                     51/37 ASN AAT MET 19 ATG 0.75 ± 0.50 (2)                                   51/37 ASN AAT PRO 19 CCG 2.77 ± 1.6 (3)                                    51/37 ASN AAT SER 19 TCC 0.87 ± 0.44 (3)                                   51/37 ASN AAT THR 19 ACG 2.3 ± 1.6 (3)                                     51/37 ASN AAT HIS 19 CAC 1.3 ± 0.9 (5)                                     52/38 ASN AAC HIS 19 CAC 0.004 (1)                                            52/38 ASN AAC ARG 19 CGC 0.004 (1)                                            52/38 ASN AAC LEU 19 TGG 0.003 (1)                                            52/38 ASN AAC GLY 19 GGC 0.22 (1)                                             52/38 ASN AAC SER 19 AGC 0.07 (1)                                             52/38 ASN AAC THR 19 ACG 0.44 ± 0.30 (3)                                   53/39 LEU CTT THR 19 ACC <0.005 (1)                                           53/39 LEU CTT ALA 19 GCG --                                                   53/39 LEU CTT GLY 19 GGC <0.005 (1)                                           53/39 LEU CTT GLU 19 GAG <0.005 (1)                                           53/39 LEU CTT PRO 19 CCG <0.005 (1)                                           53/39 LEU CTT LYS 19 AAG <0.005 (1)                                           53/39 LEU CTT SER 19 AGC 0.008 (1)                                            53/39 LEU CTT MET 19 ATG 0.31 (1)                                             54/40 ARG CGA ASP 19 GAC <0.005 (1)                                           54/40 ARG CGA ILE 19 ATC 0.05 (1)                                             54/40 ARG CGA SER 19 TCC 0.10 (1)                                             54/40 ARG CGA VAL 19 GTG <0.005 (1)                                           54/40 ARG CGA THR 19 ACC 0.015 (1)                                            54/40 ARG CGA GLN 19 CAG 0.04 (1)                                             54/40 ARG CGA LEU 19 TTG 0.03 (1)                                             55/41 ARG AGG THR 19 ACC 0.65 ± 1.1 (4)                                    55/41 ARG AGG VAL 19 GTC 0.96 ± 0.36 (3)                                   55/41 ARG AGG SER 19 TCG 0.065 (1)                                            55/41 ARG AGG LEU 19 CTG 1.1 ± 1.2 (4)                                     55/41 ARG AGG GLY 19 GGC 1.0 ± 0.6 (4)                                     56/42 PRO CCA GLY 19 GGC 1.1 ± 0.8 (3)                                     56/42 PRO CCA CYS 19 TGC 0.21 (1)                                             56/42 PRO CCA SER 19 AGC 1.4 ± 0.4 (2)                                     56/42 PRO CCA GLN 19 CAG 1.8 (1)                                              56/42 PRO CCA LYS 19 AAG 0.60 (1)                                             57/43 ASN AAC GLY.sup.4 19 GGC --                                             58/44 LEU CTG SER 19 AGC <0.041 (1)                                           58/44 LEU CTG ASP 19 GAC <0.041 (1)                                           58/44 LEU CTG ARG 19 CGG <0.041 (1)                                           59/44 LEU CTG GLN 19 CAG <0.041 (1)                                           58/44 LEU CTG VAL 19 GTC <0.041 (1)                                           58/44 LEU CTG CYS 19 TGC --                                                   59/45 GLU GAG TYR 19 TAC 0.41 ± 0.37 (5)                                   59/45 GLU GAG HIS 19 CAC 0.38 ± 0.31 (2)                                   59/45 GLU GAG LEU 19 CTC 0.46 ± 0.36 (6)                                   59/45 GLU GAG PRO 19 CCC --                                                   59/45 GLU GAG ARG 19 CGC 0.15 (1)                                             60/46 ALA GCA SER 19 AGC 0.91 ± 0.55 (4)                                   60/46 ALA GCA PRO 19 CCC --                                                   60/46 ALA GCA TYR 19 TAC <0.008 (1)                                           60/46 ALA GCA ASN 19 AAC 0.38 (1)                                             60/46 ALA GCA THR 19 ACG 0.21 (1)                                             61/47 PHE TTC ASN 19 AAC --                                                   61/47 PHE TTC GLU 19 CAG <0.010 (1)                                           61/47 PHE TTC PRO 19 CCC --                                                   61/47 PHE TTC LYS 19 AAG <0.010 (1)                                           61/47 PHE TTC ARG 19 CGC 0.006 (1)                                            61/47 PHE TTC SER 19 TCG 0.17 (1)                                             62/48 ASN AAC HIS 19 CAC --                                                   62/48 ASN AAC VAL 19 GTG 0.37 ± 0.25 (4)                                   62/48 ASN AAC ARG 19 ACG --                                                   62/48 ASN AAC PRO.sup.7 19 CCG 1.6 ± 0.4 (3)                               62/48 ASN AAC PRO 19 CCG 2.0 ± 0.3 (3)                                     62/48 ASN AAC THR.sup.8 19 ACG 2.3 ± 1.1 (3)                               62/48 ASN AAC ASP 19 GAC --                                                   62/48 ASN AAC ILE 19 ATC 0.56 ± 0.24 (4)                                   63/49 ARG A(G/A)G TYR 19 TAC 0.47 (1)                                         63/49 ARG A(G/A)G TRP 19 TGG 0.09 (1)                                         63/49 ARG A(G/A)G LYS 19 AGG 0.52 (1)                                         63/49 ARG A(G/A)G SER.sup.9 19 TCC 0.13 (1)                                   63/49 ARG A(G/A)G HIS 19 CAC 0.42 ± 0.25 (7)                               63/49 ARG A(G/A)G PRO 19 CCG <0.014 ± 0.013 (2)                            63/49 ARG A(G/A)G VAL 19 GTG 0.39 ± 0.34 (3)                               64/50 ALA GCT ASN 19 AAC 1.5 ± 2.9 (4)                                     64/50 ALA GCT PRO 19 CCG <0.023 (1)                                           64/50 ALA GCT SER 19 AGC <0.023 (1)                                           64/50 ALA GCT LYS 19 AAG <0.047 (1)                                           65/51 VAL GTC THR 19 ACC 0.71 ± 0.64 (3)                                   65/51 VAL GTC PRO 19 CCG <0.014 (1)                                           65/51 VAL GTC HIS 19 CAC <0.014 (1)                                           65/51 VAL GTC LEU 19 CTC 0.42 (1)                                             65/51 VAL GTC PHE 19 TTC 0.061 (1)                                            65/51 VAL GTC SER 19 TCC 0.34 (1)                                             66/52 LYS AAG ILE.sup.10 19 ATC 0.42 (1)                                      66/52 LYS AAG ARG 19 AGG 0.79 ± 0.18 (2)                                   66/52 LYS AAG VAL 19 GTC 0.38 ± 0.17 (2)                                   66/52 LYS AAG ASN 19 AAC 0.32 (1)                                             66/52 LYS AAG GLU 19 GAG 0.14 (1)                                             66/52 LYS AAG SER 19 TCG 0.31 (1)                                             66/52 LYS AAG VAL.sup.11 19 GTG 0.055 (1)                                     67/53 SER AGT ALA 19 GCG <0.014 (1)                                           67/53 SER AGT PHE 19 TTC 1.2 ± 0.2 (2)                                     67/53 SER AGT VAL 19 GTG 0.24 (1)                                             67/53 SER AGT GLY 19 GGG 0.50 ± 0.29 (4)                                   67/53 SER AGT ASN 19 AAC 0.52 ± 0.28 (7)                                   67/53 SER AGT ILE 19 ATC 0.29 (1)                                             67/53 SER AGT PRO 19 CCG 0.055 (1)                                            67/53 SER AGT HIS 19 CAC 0.99 ± 0.62 (6)                                   68/54 LEU TTA VAL 19 GTC 0.14 (1)                                             68/54 LEU TTA TRP 19 TGG 0.07 (1)                                             68/54 LEU TTA SER 19 AGC <0.003 (1)                                           68/54 LEU TTA ILE 19 ATC 0.84 ± 0.47 (3)                                   68/54 LEU TTA PHE 19 TTC 1.7 ± 0.3 (3)                                     68/54 LEU TTA THR 19 ACG 0.011 (1)                                            68/54 LEU TTA HIS 19 CAC 0.82 ± 0.45 (2)                                   69/55 GLN CAG ALA 19 GCG 1.2 ± 0.8 (3)                                     69/55 GLN CAG PRO 19 CCA 0.74 0.45 (4)                                        69/55 GLN CAG THR 19 ACG 0.97 ± 0.46 (4)                                   69/55 GLN CAG TRP 19 TGG --                                                   69/55 GLN CAG GLU 19 GAG 1.4 ± 0.7 (3)                                     69/55 GLN CAG ARG 19 CGG 1.4 ± 1.1 (3)                                     69/55 GLN CAG GLY 19 GGG 0.68 ± 0.02 (2)                                   69/55 GLN CAG LEU 19 CTC --                                                   70/56 ASN AA(C/T) LEU 19 TTG 0.032 (1)                                        70/56 ASN AA(C/T) VAL 19 GTG --                                               70/56 ASN AA(C/T) TRP 19 TGG --                                               70/56 ASN AA(C/T) PRO.sup.12 19 CCG 0.43 ± 0.29 (2)                        70/56 ASN AA(C/T) ALA.sup.12 19 GCC 0.03 (1)                                  71/57 ALA GCA MET 19 ATG 0.23 (1)                                             71/57 ALA GCA LEU 19 CTG <0.005 (1)                                           71/57 ALA GCA PRO 19 CCC 0.58 (1)                                             71/57 ALA GCA ARG 19 AGG 0.66 (1)                                             71/57 ALA GCA GLU 19 GAG 0.46 ± 0.27                                       71/57 ALA GCA THR 19 ACC 0.34 ± 0.41 (3)                                   71/57 ALA GCA GLN 19 GGC 0.42 ± 0.32 (3)                                   71/57 ALA GCA TRP 19 TGG --                                                   71/57 ALA GCA ASN 19 AAC 0.09 (1)                                             72/58 SER TCA GLU 19 GAG 0.62 ± 0.27 (3)                                   72/58 SER TCA MET 19 ATG 0.45 ± 0.55 (3)                                   72/58 SER TCA ALA 19 GCC 0.48 ± 0.33 (3)                                   72/58 SER TCA HIS 19 GAC 0.10 (1)                                             72/58 SER TCA ASN 19 AAC 0.38 ± 0.44 (3)                                   72/58 SER TCA ARG 19 CGG 0.81 ± 0.43 (4)                                   72/58 SER TCA ASP 19 GAC 0.58 ± 0.39 (3)                                   73/59 ALA GCA GLU 19 GAG 0.49 ± 0.32 (3)                                   73/59 ALA GCA ASP 19 GAC 0.27 (1)                                             73/59 ALA GCA LEU 19 CTG 0.55 ± 0.45 (4)                                   73/59 ALA GCA SER 19 AGC 0.37 ± 0.36 (2)                                   73/59 ALA GCA GLY 19 GGG 0.38 ± 0.32 (3)                                   73/59 ALA GCA THR 19 ACC 0.31 (1)                                             73/59 ALA GCA ARG 19 AGG 0.40 ± 0.18 (3)                                   74/60 ILE AT(T/C) MET 19 ATG <0.16 (1)                                        74/60 ILE AT(T/C) THR 19 ACG --                                               74/60 ILE AT(T/C) PRO 19 CCG --                                               74/60 ILE AT(T/C) ARG 19 AGG --                                               74/60 ILE AT(T/C) GLY 19 GGG 0.006 (1)                                        74/60 ILE AT(T/C) ALA 19 GCG --                                               75/61 GLU CAG LYS 19 AAG 0.07 ± 0.07 (2)                                   75/61 GLU CAG GLY 19 GGG 0.27 ± 0.20 (2)                                   75/61 GLU GAG ASP 19 GAC 0.18 (1)                                             75/61 GLU GAG PRO 19 CCG --                                                   75/61 GLU GAG TRP 19 TGG --                                                   75/61 GLU GAC ARG 19 CGG --                                                   75/61 GLU GAG SER 19 TCG 0.27 ± 0.22 (3)                                   75/61 GLU GAG GLN 19 CAG 0.40 ± 0.38 (3)                                   75/61 GLU GAG LEU 19 TTG --                                                   76/62 SER ACC VAL 19 GTG 1.0 ± 0.2 (2)                                     76/62 SER ACC ALA 19 GCG 0.94 ± 0.46 (2)                                   76/62 SER ACC ASN 19 AAC 1.2 (1)                                              76/62 SER AGC TRP 19 TCG --                                                   76/62 SER AGC GLU 19 GAG 0.90 ± 0.19 (2)                                   76/62 SER AGC PRO 19 CCG 2.1 ± 0.8 (4)                                     76/62 SER AGC GLY 19 GGC 1.3 ± 1.0 (4)                                     76/62 SER AGC ASP 19 GAC 0.29 (1)                                             77/63 ILE ATT SER 19 AGC 0.48 ± 0.38 (4)                                   77/63 ILE ATT ARG 19 CGC 0.09 ± 0.04 (2)                                   77/63 ILE ATT THR 19 ACG <0.008 (1)                                           77/63 ILE ATT LEU 19 TTG 2.0 ± 0.1 (3)                                     78/64 LEU CTT ALA 19 GCG --                                                   75/64 LEU CTT SER 19 TCC --                                                   78/64 LEU CTT GLU 19 GAG <0.006 (1)                                           78/64 LEU CTT PRE 19 TTC --                                                   78/64 LEU CTT GLY 19 GGG --                                                   78/64 LEU CTT ARG 19 AGG --                                                   79/65 LYS AA(A/G) THR 19 ACA 0.77 ± 0.91 (6)                               79/65 LYS AA(A/G) GLY 19 CGC 1.1 ± 0.9 (6)                                 79/65 LYS AA(A/G) ASN 19 AAC 1.0 ± 0.6 (6)                                 79/65 LYS AA(A/G) MET 19 ATG 1.6 ± 0.7 (6)                                 79/65 LYS AA(A/G) ARG 19 CGC 1.04 ± 0.7 (7)                                79/65 LYS AA(A/G) ILE 19 ATC 1.0 ± 0.6 (6)                                 79/65 LYS AA(A/G) GLY 19 GGG 1.2 ± 0.4 (6)                                 79/65 LYS AA(A/G) ASP 19 GAC 0.72 ± 0.38 (7)                               80/66 ASN AAT TRP 19 TGG --                                                   80/66 ASN AAT VAL 19 GTC 0.32 (1)                                             80/66 ASN AAT GLY 19 GGC 1.5 ± 1.4 (4)                                     80/66 ASN AAT THR 19 ACG 0.13 (1)                                             80/66 ASN AAT LEU 19 CTG 0.33 ± 0.14 (2)                                   80/66 ASN AAT GLU 19 GAG 1.1 ± 0.8 (4)                                     80/66 ASN AAT ARG 19 AGG 1.0 ± 0.8 (4)                                     81/67 LEU CTC GLN 19 CAA --                                                   81/67 LEU CTC GLY 19 GGC <0.023 (1)                                           81/67 LEU CTC ALA 19 GCG <0.047 (1)                                           81/67 LEU CTC TRP 19 TGG <0.005 (1)                                           81/67 LEU CTC ARG 19 CGG --                                                   81/67 LEU CTC VAL 19 GTG 0.16 ± 0.18 (2)                                   81/67 LEU CTC LYS 19 AAG --                                                   82/68 LEU C(TG/CC) GLN 19 CAG 1.8 ± 0.3 (3)                                82/68 LEU C(TG/CC) LYS 19 AAG 0.05 (1)                                        82/68 LEU C(TG/CC) TRP 19 TGG 2.7 ± 1.3 (4)                                82/68 LEU C(TG/CC) ARG 19 AGC 1.1 ± 0.2 (3)                                82/68 LEU C(TG/CC) ASP 19 GAC 2.7 ± 1.3 (4)                                82/68 LEU C(TG/CC) VAL 19 GTG 1.5 ± 1.1 (5)                                83/69 PRO CCA ALA 19 GCA 0.41 (1)                                             83/69 PRO CCA THR 19 ACC 0.66 ± 0.12 (3)                                   83/69 PRO CCA ARG 19 CGG --                                                   83/69 PRO CCA TRP 19 TGG 0.29 (1)                                             83/69 PRO CCA MET 19 ATG 0.43 ± 0.28 (3)                                   84/70 CYS TG(T/C) GLU 19 GAG <0.014 (1)                                       84/70 CYS TG(T/C) GLY 19 GGG <0.006 (1)                                       84/70 CYS TG(T/C) ARG 19 AGG --                                               84/70 CYS TG(T/C) MET 19 ATG --                                               84/70 CYS TG(T/C) VAL 19 GTG --                                               85/71 LEU CTG ASN 19 AAC --                                                   85/71 LEU CTG VAL 19 GTG 0.52 ± 0.21 (5)                                   85/71 LEU CTG CLN 19 CAG --                                                   86/72 PRO CCC CYS 19 TGC --                                                   86/72 PRO CCC ARG 19 AGG --                                                   86/72 PRO CCC ALA 19 GCG --                                                   86/72 PRO CCC LYS 19 AAG --                                                   87/73 LEU (C/A)TG SER 19 AGC 1.5 ± 0.4 (3)                                 87/73 LEU (C/A)TG TRP 19 TGG --                                               87/73 LEU (C/A)TG GLY 19 GGG --                                               88/74 ALA GCC LYS 19 AAG --                                                   88/74 ALA GCC ARG 19 AGG 0.11 ± 0.10 (2)                                   88/74 ALA GCC VAL 19 GTG 0.09 ± 0.02 (2)                                   88/74 ALA GCC TRP 19 TGG 1.8 ± 0.2 (2)                                     89/75 THR AC(G/A) ASP 19 GAC 0.24 ± 0.10 (2)                               89/75 ThR AC(G/A) CYS 19 TGC --                                               89/75 THR AC(G/A) LEU 19 CTC 0.01 (1)                                         89/75 THR AC(G/A) VAL 19 GTG 0.08 (1)                                         89/75 THR AC(G/A) GLU 19 GAG 0.11 (1)                                         89/75 THR AC(G/A) HIS 19 CAC 0.16 ± 0.06 (2)                               89/75 THR AC(C/A) ASN 19 AAC 0.21 ± 0.04 (2)                               89/75 THR AC(G/A) SER 19 TCG 0.25 ± 0.07 (2)                               90/76 ALA GCC PRO 19 CCC 0.03 (1)                                             90/76 ALA GCC SER 19 TCG --                                                   90/76 ALA GCC THR 19 ACC 0.48 (1)                                             90/76 ALA GCC GLY 19 GGC <0.006 (1)                                           90/76 ALA GCC ASP 19 GAC 0.44 ± 0.29 (4)                                   90/76 ALA GCC TLE 19 ATC --                                                   90/76 ALA GCC MET 19 ATG 0.25 ± 0.13 (2)                                   91/77 ALA CCA PRO 19 CCC 1.9 ± 1.2 (3)                                     91/77 ALA GCA SER 19 TCC 0.12 ± 0.07 (2)                                   91/77 ALA GCA THR 19 ACC 0.48 ± 0.16 (2)                                   91/77 ALA GCA PHE 19 TTC 0.44 ± 0.50 (3)                                   91/77 ALA GCA LEU 19 CTC 0.43 ± 0.27 (5)                                   91/77 ALA GCA ASP 19 GAC 0.55 ± 0.09 (2)                                   91/77 ALA GCA HIS 19 GAC --                                                   92/78 PRO CCC PHE 19 TTC --                                                   92/78 PRO CCC ARG 19 CGG --                                                   92/78 PRO CCC SER 19 AGC 0.26 (1)                                             92/78 PRO CCC LYS 19 AAG --                                                   92/78 PRO CCC HIS 19 CAC --                                                   92/78 PRO CCC LEU 19 CTG --                                                   93/79 THR ACG ASP 19 GAC 1.3 ± 0.7 (4)                                     93/79 THR ACG SER 19 TCG 0.70 ± 0.56 (4)                                   93/79 THR ACG ASN 19 AAC --                                                   93/79 THR ACG PRO 19 CCC 0.53 ± 0.36 (4)                                   93/79 THR ACG ALA 19 GCG 1.13 ± 0.2 (3)                                    93/79 THR ACG LEU 19 CTG 0.69 ± 0.42                                       93/79 THR ACG ARG 19 CGC 0.93 ± 0.96 (4)                                   94/80 ARG CGA ILE 19 ATC <0.020 (1)                                           94/80 ARG CGA SER 19 TCC <0.100 (1)                                           94/80 ARC CCA GLU 19 GAG <0.020 (1)                                           94/80 ARG CGA LEU 19 CTG <0.020 (1)                                           94/80 ARC CGA VAL 19 GTG <0.024 (1)                                           94/80 ARG CGA PRO 19 CCC <0.024 (1)                                           95/81 HIS CAT GLN 19 CAG <0.010 (1)                                           95/81 HIS CAT PRO 19 CCG 1.6 ± 0.8 (3)                                     95/81 HIS CAT ARG 19 CGC 4.7 ± 5.9 (2)                                     95/81 HIS CAT VAL 19 GTC 1.2 ± 1.7 (2)                                     95/81 HIS CAT LEU 19 CTC 0.7 (1)                                              95/81 HIS CAT GLY 19 GGC 1.7 ± 2.4 (5)                                     95/81 HIS CAT THR 19 ACC 2.9 ± 4.5 (4)                                     95/81 HIS CAT TYR 19 TAC 0.07 (1)                                             96/82 PRO CCA LYS 19 AAG <0.010 ± 0.001 (2)                                96/82 PRO CCA TYR 19 TAC 0.69 (1)                                             96/82 PRO CCA GLY 19 GGG <0.040 (1)                                           96/82 PRO CCA ILE 19 ATC <0.040 (1)                                           96/82 PRO CCA THR 19 ACC <0.040 (1)                                           97/83 ILE ATC VAL 19 GTC 0.91 ± 1.2 (8)                                    97/83 ILE ATC LYS 19 AAG <0.024                                               97/83 ILE ATC ALA 19 GCG 0.15 (1)                                             97/63 ILE ATC ASN 19 AAT <0.02 (1)                                            98/84 HIS CAT ILE 19 ATC 5.0 ± 4.9 (12)                                    98/84 HIS CAT ASN 19 AAC 1.4 ± 0.4 (2)                                     98/84 HIS CAT LEU 19 CTC 2.4 ± 1.0 (2)                                     98/84 HIS CAT ASP 19 GAC 0.38 ± 0.49 (5)                                   98/84 HIS CAT ALA 19 GCC 2.0 ± 1.0 (3)                                     98/84 HIS CAT THR 19 ACG 1.6 ± 0.3 (2)                                     98/84 HIS CAT LEU 19 TTG 1.5 (1)                                              98/84 HIS CAT PRO 19 CCG 0.55 (1)                                             99/85 ILE ATC LEU 19 CTG 1.4 ± 1.4 (7)                                     99/85 ILE ATC ARG 19 CGC <0.025 (1)                                           99/85 ILE ATC ASP 19 GAC <0.025 (1)                                           99/85 ILE ATC VAL 19 GTC 0.51 ± 0.59 (3)                                   99/85 ILE ATC PRO 19 CCG <0.025 (1)                                           99/85 ILE ATC GLN 19 CAG <0.018 ± 0.010 (2)                                99/85 ILE ATC GLY 19 GGG <0.018 ± 0.10 (2)                                 99/85 ILE ATC SER 19 TCG <0.025 (1)                                           99/85 ILE ATC PHE 19 TTC 0.45 (1)                                             99/85 ILE ATC HIS 19 cAC <0.025 (1)                                           100/86 LYS AAG TYR 19 TAC 0.03 (1)                                            100/86 LYS AAG LEU 19 TTG 0.33 ± 0.31 (3)                                  100/86 LYS AAG HIS 19 CAC 0.36 ± 0.22 (9)                                  100/86 LYS AAG ARG 19 AGC 4.7 ± 5.9 (4)                                    100/86 LYS AAG ILE 19 ATC 0.95 (1)                                            100/86 LYS AAG SER 19 AGC 0.95 (1)                                            100/86 LYS AAG GLN 19 CAG 0.78 ± 0.80 (7)                                  100/86 LYS AAG PRO 19 CCG 0.70 (1)                                            101/87 ASP GAC PRO 19 CCC 2.3 ± 3.1 (4)                                    101/87 ASP GAC MET 19 ATG 1.8 ± 2.5 (6)                                    101/87 ASP GAC LYS 19 AAG 1.2 ± 1.7 (3)                                    101/87 ASP GAC HIS 19 CAC 2.5 (1)                                             101/87 ASP GAC ThR 19 ACG 0.90 ± 0.77 (3)                                  101/87 ASP GAC TYR 19 TAC 0.59 (1)                                            101/87 ASP GAC VAL 19 GTC 0.42 (1)                                            101/87 ASP GAC TYR 19 TAC 1.0 ± 0.02 (2)                                   101/67 ASP GAC GLN 19 CAG 0.07 (1)                                            102/88 GLY GGT LEU 19 CTC <0.015 ± 0.007 (2)                               102/88 GLY GGT GLU 19 GAG 0.40 ± 0.07 (3)                                  102/88 GLY GGT LYS 19 AGG 0.16 ± 0.14 (2)                                  102/88 GLY GGT SER 19 TCC 0.29 (1)                                            102/88 GLY GGT TYR 19 TAC 0.04 (1)                                            102/88 GLY GGT PRO 19 CCC <0.011 (1)                                          103/89 ASP GAC SER 19 TCC 0.02 (1)                                            104/90 TRP TGG VAL 19 GTG 0.11 ± 0.06 (5)                                  104/90 TRP TGG CYS 19 AGC 0.07 ± 0.03 (5)                                  104/90 TRP TGG TYR 19 TAC 0.34 ± 0.42 (5)                                  104/90 TRP TGG THR 19 ACC 0.04 ± 0.02 (2)                                  104/90 TRP TGG MET 19 ATG 0.14 (1)                                            104/90 TRP TGG PRO 19 CCC 0.02 ± 0.02 (2)                                  104/90 TRP TGG LEU 19 TTG 0.65 ± 1.0 (3)                                   104/90 TRP TGG GLN 19 CAG 0.008 (1)                                           104/90 TRP TGG LYS 19 AAG --                                                  104/90 TRP TGG GLY 19 GAG --                                                  104/90 TRP TGG ALA 19 GCC --                                                  104/90 TRP TGG PHE 19 TTC --                                                  104/90 TRP TGG GLY 19 GGC --                                                  105/91 ASN AAT PRO 19 CCG 4.8 ± 8.5 (5)                                    105/91 ASN AAT ALA 19 GCC 0.65 ± 0.30 (3)                                  105/91 ASN AAT PHE 19 TTC 0.13 (1)                                            105/91 ASN AAT SER 19 TCC 1.9 ± 2.7 (5)                                    105/91 ASN AAT TRP 19 TGG 0.95 (1)                                            105/91 ASN AAT GLN 19 CAA 0.57 ± 0.52 (3)                                  105/91 ASN AAT TYR 19 TAC 0.66 ± 0.53 (4)                                  105/91 ASN AAT LEU 19 CTC 0.87 ± 0.79 (2)                                  105/91 ASN AAT LYS 19 AAG 0.70 (1)                                            105/91 ASN AAT ILE 19 ATC 1.0 (1)                                             105/91 ASN AAT ASP 19 GAC 1.0 ± 0.9 (4)                                    105/91 ASN AAT HIS 19 CAC 0.71 ± 0.48 (2)                                  106/92 GLU GAA SER 19 TCC 0.17 ± 0.21 (2)                                  106/92 GLU GAA ALA 19 GCG 0.235 ± 0.26 (2)                                 106/92 GLU GAA LYS 19 AAG --                                                  106/92 GLU GAA THR 19 ACC --                                                  106/92 GLU GAA ILE 19 ATC --                                                  106/92 GLU GAA GLY 19 GGC 0.70 ± 0.76 (4)                                  106/92 GLU GAA PRO 19 CCC --                                                  108/94 ARG CGG LYS 19 AAG 0.11 ± 0.03 (2)                                  108/94 ARG CGG ASP 19 GAC --                                                  105/94 ARG CGG LEU 19 TTG 0.01 (1)                                            108/94 ARG CGG THR 19 ACG 0.08 (1)                                            106/94 ARG CGG ILE 19 ATC <0.01 (1)                                           106/94 ARG CGG PRO 19 CCC --                                                  109/95 ARG AGG THR 19 ACC 1.1 ± 0.2 (3)                                    109/95 ARG AGG PRO 19 CCC --                                                  109/95 ARG ACG GLU 19 GAG 1.1 ± 0.1 (3)                                    109/95 ARG ACG TYR 19 TAC <0.006 (1)                                          109/95 ARG AGG LEU 19 CTC 1.2 ± 0.9 (4)                                    109/95 ARG AGG SER 19 TCG 1.7 ± 0.8 (4)                                    109/95 ARG AGG GLY 19 GGG 0.17 (1)                                            110/96 LYS AAA ALA 19 GCC <0.08 (1)                                           110/96 LYS AAA ASN 19 AAC --                                                  110/96 LYS AAA THR 19 ACG --                                                  110/96 LYS AAA LEU 19 CTC --                                                  110/96 LYS AAA ARG 19 CGG --                                                  110/96 LYS AAA GLN 19 CAG --                                                  110/96 LYS AAA TRP 19 TGG --                                                  111/97 LEU CTG ILE 19 ATC --                                                  111/97 LEU CTG ARG 19 CGG --                                                  111/97 LEU CTG ASP 19 GAC --                                                  111/97 LEU CTG MET 19 ATG --                                                  112/98 THR ACG VAL 19 GTG 0.55 ± 0.44 (3)                                  112/98 THR ACG GLN 19 CAG 1.7 ± 1.0 (3)                                    112/98 THR ACG TYR 19 TAC <0.018 (1)                                          112/98 THR ACG GLU 19 GAG 0.12 (1)                                            112/98 THR ACG HIS 19 CAC 0.25 ± 0.40 (3)                                  112/98 THR ACG SER 19 TCC 0.17 ± 0.15 (2)                                  112/98 THR ACG PHE 19 TTC --                                                  113/99 PHE TTC SER 19 AGC --                                                  113/99 PHE TTC CYS 19 TGC --                                                  113/99 PHE TTC HIS 19 CAC <0.009 (1)                                          113/99 PHE TTC GLY 19 GGC --                                                  113/99 PHE TTC TRP 19 TGG --                                                  113/99 PHE TTC TYR 19 TAC 0.07 (1)                                            113/99 PHE TTC ASN 19 AAC --                                                  114/100 TYR TAT CYS 19 TGC --                                                 114/100 TYR TAT HIS 19 CAC --                                                 114/100 TYR TAT SER 19 AGC --                                                 114/100 TYR TAT TRP 19 TGG 0.88 (1)                                           114/100 TYR TAT ARG 19 AGG --                                                 114/100 TYR TAT LEU 19 CTC <0.018 (1)                                         115/101 LEU CTG ASN 19 AAC <0.004 (1)                                         115/101 LEU CTG VAL 19 GTG --                                                 115/101 LEU CTG PRO 19 CCC <0.004                                             115/101 LEU CTG ARG 19 AGG <0.004 (1)                                         115/101 LEU CTG ALA 19 GCG 0.50 (1)                                           115/101 LEU CTG HIS 19 CAC --                                                 115/101 LEU CTG THR 19 ACC --                                                 115/101 LEU CTG TRP 19 TGG --                                                 115/101 LEU CTG MET 19 ATG <0.008 (1)                                         116/102 LYS AAA LEU.sup.14 19 TTG --                                          116/102 LYS AAA PRO.sup.14 19 CCG <0.004 (1)                                  116/102 LYS AAA THR.sup.14 19 ACC 0.50 (1)                                    116/102 LYS AAA MET.sup.14 19 ATG 0.13 (1)                                    116/102 LYS AAA ASP.sup.14 19 GAC <0.018 (1)                                  116/102 LYS AAA VAL 19 GTG 2.3 ± 1.2 (5)                                   116/102 LYS AAA GLU 19 GAG 0.06 (1)                                           116/102 LYS AAA ARG 19 CGC 0.06 (1)                                           116/102 LYS AAA TRP 19 TGG 2.3 ± 1.0 (4)                                   116/102 LYS AAA SER 19 TCG 0.69 ± 0.51 (5)                                 116/102 LYS AAA LEU 19 CTC 0.14 ± 0.02 (2)                                 116/102 LYS AAA ILE 19 ATC 1.3 ± 0.3 (3)                                   116/102 LYS AAA THR 19 ACG 0.84 ± 0.30 (4)                                 117/103 THR ACC SER 19 AGC 1.1 ± 0.2 (3)                                   117/103 THR ACC ASN 19 AAC 0.31 ± 0.39 (3)                                 117/103 THR ACC ILE 19 ATC --                                                 117/103 THR ACC TRP 19 TGG 0.02 (1)                                           117/103 THR ACC LYS 19 AAG <0.005 (1)                                         117/103 THR ACC PRO 19 CCG --                                                 118/104 LEU CTT SER 19 TCA --                                                 118/104 LEU CTT PRO 19 CCC --                                                 118/104 LEU CTT ALA 19 GCC --                                                 118/104 LEU CTT GLU 19 GAG --                                                 118/104 LEU CTT CYS 19 TGC --                                                 118/104 LEU CTT ASP 19 GAC --                                                 118/104 LEU CTT TYR 19 TAC --                                                 119/105 GLU GAG SER 19 TCC 0.26 ± 0.19 (2)                                 119/105 GLU GAG LYS 19 AAG 0.04 (1)                                           119/105 GLU GAG PRO 19 CCG 0.31 ± 0.27 (3)                                 119/105 GLU GAG LEU 19 CTG 0.35 ± 0.35 (3)                                 119/105 GLU GAG THR 19 ACC 0.25 ± 0.27 (3)                                 119/105 GLU GAG TYR 19 TAC 0.30 ± 0.32 (3)                                 119/105 GLU GAG ARG 19 CGC 0.06 (1)                                           120/106 ASN AAT ALA 19 GCC <0.009 (1)                                         120/106 ASN AAT PRO 19 CCC 1.7 ± 0.7 (3)                                   120/106 ASN AAT LEU 19 TTG 1.2 ± 0.3 (3)                                   120/106 ASN AAT HIS 19 CAC 1.0 ± 0.3 (2)                                   120/106 ASN AAT VAL 19 GTG 1.7 ± 0.3 (3)                                   120/106 ASN AAT GLN 19 CAG 0.85 ± 0.16 (2)                                 120/107 ALA GCG SER 19 AGC 1.2 ± 0.2 (3)                                   120/107 ALA GCG ILE 19 ATC 2.8 ± 2.5 (2)                                   121/107 ALA GCG ASN 19 AAC 0.91 ± 0.77 (5)                                 121/107 ALA GCG PRO 19 CCG 1.3 (1)                                            121/107 ALA GCG LYS 19 AAG 0.26 ± 0.24 (2)                                 121/107 ALA GCG ASP 19 GAC 1.8* ± 0.9 (3)                                  121/107 ALA GCG GLY 19 GGC 0.69 (1)                                           122/108 GLN GCG SER 19 AGC 0.96 ± 0.41 (3)                                 122/108 GLN CA(G/A) MET 19 ATG 1.7 ± 0.5 (3)                               122/108 GLN CA(G/A) TRP 19 TGG 1.4 (1)                                        122/108 GLN CA(G/A) ARG 19 AGG 0.78 (1)                                       122/108 GLN CA(G/A) PHE 19 TTC 2.3 ± 1.1 (3)                               122/108 GLN CA(G/A) PRO 19 CCG 1.0 (1)                                        122/108 GLN CA(G/A) HIS 19 CAC 1.4 (1)                                        122/108 GLN CA(G/A) ILE 19 ATC 2.7 ± 0.8 (3)                               122/108 GLN CA(G/A) TYR 19 TAC 1.7 ± 0.3 (2)                               122/108 GLN CA(G/A) CYS 19 TGC 0.58 (1)                                       123/109 ALA GCT MET 19 ATG 2.0 ± 0.2 (3)                                   123/109 ALA GCT GLU 19 GAG 2.1 ± 1.0 (3)                                   123/109 ALA GCT HIS 19 CAC 0.98 ± 0.72 (3)                                 123/109 ALA GCT SER 19 AGC 1.4 ± 0.8 (3)                                   123/109 ALA GCT PRO 19 CCC 0.64 ± 0.16 (2)                                 123/109 ALA GCT TYR 19 TAC 0.51 ± 0.25 (2)                                 123/109 ALA GCT LEU 19 CTG 1.2 ± 0.1 (2)                                 ______________________________________                                         .sup.1 The first position number representes the amino acid position in       (1-133)hIL3 and the second number represents the position in (15-125)hIL3     in which the Asn at position 15 of native hIL3 is position 1 in               (15-125)hIL3 (See the numbering for Formula XI)                               .sup.2 Double mutant; has PRO at position 35.                                 .sup.3 Double mutant; has THR at position 49.                                 .sup.4 Double mutant; has Gly at position 32.                                 .sup.5 Double mutant; has Leu at position 31.                                 .sup.6 Double mutant; has Gly at position 46.                                 .sup.7 Double mutant; Arg at position 42.                                     .sup.8 Double mutant; Phe at position 53.                                     .sup.9 Double mutant; has Val at position 49.                                 .sup.10 Double mutant; has Pro at position 73.                                .sup.11 Double mutant; has Thr at position 64.                                .sup.12 Double mutant: has Pro at position 73.                                .sup.13 Double mutant: has Met at position 74.                                .sup.14 Double mutant: has Ser at position 105.                          

The mutants in Table 6 were made as described in the Examples,particularly Examples 19, 20, 21 and 38 to 53.

It will be apparent to those skilled in the art that other codonsbesides those shown in Table 6 can also code for the substituted aminoacids in the hIL-3 muteins. The present invention includes the DNAsencoding the mutant hIL-3 polypeptides of the invention including thevarious codons which can code for the parental and substituted aminoacids of the hIL-3 muteins of the invention due to the degeneracy of thegenetic code.

hIL-3 (15-125) variant genes encoding the variants listed in Table 6 canalso be expressed from intracellular expression vectors to produce largequantities of the variant protein which can be purified and assayed forbiological activity. The hIL-3 variant genes, from Table 6, can beexcised from the secretion expression vector, as a 345 base pairNcoI/HindIII fragment and ligated into an appropriate intracellularexpression vector, such as pMON2341 digested with NcoI and HindIII.Examples of variants transferred to pMON2341 in this manner are shown inTable 7. Two examples of such a transfer are described in theconstruction of pMON13215 (EXAMPLE 64) and pMON13252 (EXAMPLE 65).

EXAMPLE 64

Construction of pMON13215

Plasmid, pMON2341, DNA was digested with restriction enzymes NcoI andHindIII resulting in a 3619 base pair NcoI/HindIII fragment. The geneticelements derived from pMON2341 are the beta-lactamase gene (AMP), pBR327origin of replication, F1 phage origin of replication as thetranscription terminator, precA, g10L ribosome binding site. The plasmidencoding the hIL-3 (15-125) Trp.sup.(116) variant, from Table 6 wasdigested with NcoI and HindIII resulting in a 345 base pair NcoI/HindIIIfragment. The 345 Base pair NcoI/HindIII fragment was ligated with the3619 base pair fragment from pMON2341 and the ligation reaction mixturewas used to transform E. coli K-12 strain JM101. Plasmid DNA wasisolated and screened by restriction anaylsis using NcoI and HindIII.Positive clones contained a 345 base pair NcoI/HindIII. This constructwas designated PMON13215. The plasmid, pMON13215, encodes the (15-125)hIL-3 variant with the following amino acid sequence:

    PEPTIDE A9;   (15-125)HIL-3 TRP.sup.(116)  PMON13215                             -         Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu [SEQ ID                                                       NO:217]                                15                  20                  25                             - Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly                        30                  35                  40                             - Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn                        45                  50                  55                             - Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser                        60                  65                  70                             - Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu                        75                  80                  85                             - Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly                        90                  95                  100                            - Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Trp Thr                        105                 110                 115                            - Leu Glu Asn Ala Gln Ala Gln Gln -         120                 125                                                           - DNA sequence #A9                                                          pMON13215   116w                                                                - ATGGCTAACT GCTCTAACAT                                                      GATCGATGAA ATCATCACCC                                                        ACCTGAAGCA[SEQ ID                                                             NO:220]                         - GCCACCGCTG CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG                      - ATATCCTGAT GGAAAATAAC CTTCGTCGTC CAAACCTCGA GGCATTCAAC                      - CGTGCTGTCA ACTCTCTGCA GAATGCATCA GCAATTGAGA GCATTCTTAA                      - AAATCTCCTG CCATGTCTGC CCCTGGCCAC GGCCGCACCC ACGCGACATC                      - CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC                      - TTCTATCTGT GGACCTTGGA GAACGCGCAG GCTCAACAG                           

EXAMPLE 65

Construction of pMON13252

Plasmid, pMON2341, DNA was digested with restriction enzymes NcoI andHindIII resulting in a 3619 base pair NcoI/HindIII fragment. The geneticelements derived from pMON2341 are the beta-lactamase gene (AMP), pBR327origin of replication F1 phage origin of replication as thetranscription terminator, precA, g10L ribosome binding site. The plasmidencoding the hIL-3 (15-125) Asp.sup.(50) variant, from Table 6, wasdigested with NcoI and HindIII resulting in a 345 base pair NcoI/HindIIIfragment. This 345 Base pair NcoI/HindIII fragment was ligated with the3619 base pair fragment from pMON2341 and the ligation reaction mixturewas used to transform E. coli K-12 strain JM101. Plasmid DNA wasisolated and screened by restriction analysis using NcoI and HindIII.Positive clones contained a 345 base pair NcoI/HindIII. This constructwas designated pMON13252. The plasmid, pMON13252, encodes the (15-125)hIL-3 variant with the following amino acid sequence:

    PEPTIDE A10;   (15-125)HIL-3 ASP.sup.(50)  pMON13252                             -         Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu [SEQ ID                                                       NO:218]                                15                  20                  25                             - Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly                        30                  35                  40                             - Glu Asp Gln Asp Ile Leu Met Asp Asn Asn Leu Arg Arg Pro Asn                        45                  50                  55                             - Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser                        60                  65                  70                             - Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu                        75                  80                  85                             - Ala Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp Gly                        90                  95                  100                            - Asp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys Thr                        105                 110                 115                            - Leu Glu Asn Ala Gln Ala Gln Gln                                                    120                 125                                                - DNA sequence #A10 pMON13252   50D                                           - ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA[SEQ ID                                                             NO:216]                         - GCCACCGCTG CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG                      - ATATCCTGAT GGAAAATAAC CTTCGTCGTC CAAACCTCGA GGCATTCAAC                      - CGTGCTGTCA ACTCTCTGCA GAATGCATCA GCAATTGAGA GCATTCTTAA                      - AAATCTCCTG CCATGTCTGC CCCTGGCCAC GGCCGCACCC ACGCGACATC                      - CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TAAACTGACC                      - TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAG                           

                                      TABLE 7                                     __________________________________________________________________________           position/                                                                 mutant NATIVE SUBSTITUTION  RELATIVE                                         pMON number (15-125) hIL-3 amino acid amino acid SEQ ID NO: POTENCY         __________________________________________________________________________    pMON13201                                                                            45/31M Gln   Met     19    6.3                                           pMON13202 51/37R Asn Arg 19 1.58                                              pMON13203 51/37P Asn Pro 19 2.5                                               pMON13204 51/37T Asn Thr 19 3.16                                              pMON13205 56/42S Pro ser 19 6.3                                               pMON13206 98/84I His Ile 19 6.3                                               pMON13207 45/31V Gln Val 19 4                                                 pMON13208 42/28D Gly Asp 19 6.3                                               pMON13209 42/28S Gly Ser 19 12.6                                              pMONI3210 42/28A Gly Ala 19 2.5                                               pMON13211 46/32S Asp Ser 19 16                                                pMON13212 82/68W Leu Trp 19 5                                                 pMON13213 82/680 Leu Asp 19 4                                                 pMON13214 100/86R Lys Arg 19 4                                                pMON13215 116/102W Lys Trp 19 31                                              pMON13216 23/9L Ile Leu 19 4                                                  pMON13217 32/18R Leu Arg 19 7.9                                               pMON13218 32/18N Leu Asn 19 2                                                 pMON13219 32/18A Leu Ala 19 1.58                                              pMON13220 34/20S Leu Ser 19 6.3                                               pMON13221 34/20M Leu Met 19 6.3                                               pMON13222 50/36D Glu Asp 19 7.9                                               pMON13223 162/48I Asn Ile 19 *                                                pMON13224 66/52R Lys Arg 19 4                                                 pMON13225 76/62P Ser Pro 19 1.25                                              pMON13226 77/63L Ile Leu 19 1.58                                              pMON13227 22/8G Glu Gly 19 0.008                                              pMON13228 115/101M Leu Met 19 0.04                                            pMON13229 122/1081 Gln Ile 19 1                                               pMON13231 51/37H Asn His 19 1.25                                              pMON13232 59/45L Glu Leu 19 1.99                                              pMON13233 63/49H Arg His 19 *                                                 pMON13234 64/50N Ala Asn 19 0.03                                              pMON13235 65/51T Val Thr 19 1.58                                              pMON13236 76/62V Ser Val 19 2.5                                               pMON13237 76/62A Ser Ala 19 5                                                 pMON13238 91/77P Ala Pro 19 *                                                 pMON13240 100/860 Lys Gln 19 2.5                                              pMON13241 101/87M Asp Met 19 6.3                                              pMON13242 105/91N Asn Asn 19 *                                                pMON13243 116/102V Lys Val 19 7.9                                             pMON13244 122/108F Gln Phe 19 6.3                                             pMON13245 123/109E Ala Glu 19 1.58                                            pMON13246 42D Gly Asp 15 20                                                   pMON13247 42S Gly Ser 15 *                                                    pMON13248 42A Gly Ala 15 16                                                   pMON13249 45V Gln Val 15 5                                                    pMON13250 45M Gln Met 15 *                                                    pMON13251 46S Asp Ser 15 5                                                    pMON13252 50D Glu Asp 15 5                                                    pMON13253 98I His Ile 15 *                                                    pMON13264 97V Ile Val 15 4                                                    pMON13266 75K Glu Lys 15 0.25                                                 pMON13267 89N Thr Asn 15 2.5                                                __________________________________________________________________________

Table 7 shows the biological activity of (15-125) hIL-3 mutantpolypeptides of the present invention expressed from intracellularexpression vectors. Upon expression these muteins may have Met- orMet-Ala-preceding the initial (15-125) hIL-3 amino acid. The relativebiological activity of IL-3 mutants is calculated by dividing the EC₅₀(1-133) hIL-3 by the EC₅₀ of the mutant.

EXAMPLE 66

The variants in Table 8 were constructed by cassette mutagenesis usingmethods described in the Materials and Methods and the Examplescontained herein, particularly Examples 54-57. Parental plasmid DNA(Table 8), digested with the appropriate restriction enzymes (Table 8),was ligated with the indicated annealed pairs of complementaryoligonucleotides (Table 8). The assembled oligonucleotides createappropriate restriction ends and a portion of the (15-125) hIL-3 genesequence Individual isolates were screened by restriction analysis andDNA sequenced to confirm that the desired changes in the (15-125) hIL-3variant gene were made. The oligonucleotides create change(s) in the(15-125) hIL-3 gene which enclode the corresponding amino acidsubstitution in the variant polypeptide (Table 8). The amino acidssubstitutions in polypeptide #1 (SEQ ID NO:65) are indicated in Table 8.

                                      TABLE 8                                     __________________________________________________________________________    position/native a.a.                                                                   substitution                                                                         codon                                                                             oligo pair                                                                             oligo pair                                                                            oligo pair                                                                             oligo pair                                                                            oligo pair              __________________________________________________________________________      21 asp glu GAA 21glu1 NcoRv2 NcoRV3                                              SEQ ID NO:73 SEQ ID NO:523 SEQ ID NO:524                                      21glu4 NcoRV5 NcoRV6                                                          SEQ ID NO:219 SEQ ID NO:526 SEQ ID NO:527                                  21 asp gln CAA 21gln1 NcoRv2 NcoRV3                                              SEQ ID NO:71 SEQ ID NO:523 SEQ ID NO:524                                      21gln4 NcoRV5 NcoRV6                                                          SEQ ID NO:72 SEQ ID NO:526 SEQ ID NO:527                                   21 asp asn AAC 21asn1 NcoRv2 NcoRV3                                              SEQ ID NO:66 SEQ ID NO:523 SEQ ID NO:524                                      21asn4 NcoRV5 NcoRV6                                                          SEQ ID NO:70 SEQ ID NO:526 SEQ ID NO:527                                   21 asp thr ACC 21thr1 NcoRv2 NcoRV3                                              SEQ ID NO:232 SEQ ID NO:523 SEQ ID NO:524                                     21thr4 NcoRV5 NcoRV6                                                          SEQ ID NO:233 SEQ ID NO:526 SEQ ID NO:527                                  21 asp ser AGC 21ser1 NcoRv2 NcoRV3                                              SEQ ID NO:230 SEQ ID NO:523 SEQ ID NO:524                                     21ser4 NcoRV5 NcoRV6                                                          SEQ ID NO:231 SEQ ID NO:526 SEQ ID NO:527                                  22 glu asp GAC 22asp1 NcoRv2 NcoRV3                                              SEQ ID NO:236 SEQ ID NO:523 SEQ ID NO:524                                     22asp4 NcoRV5 NcoRV6                                                          SEQ ID NO:237 SEQ ID NO:526 SEQ ID NO:527                                  22 glu asn AAC 22asn1 NcoRv2 NcoRV3                                              SEQ ID NO:234 SEQ ID NO:523 SEQ ID NO:524                                     22asn4 NcoRV5 NcoRV6                                                          SEQ ID NO:236 SEQ ID NO:526 SEQ ID NO:527                                  22 glu gln CAG 22gln1 NcoRv2 NcoRV3                                              SEQ ID NO:236 SEQ ID NO:523 SEQ ID NO:524                                     22gln4 NcoRV5 NcoRV6                                                          SEQ ID NO:239 SEQ ID NO:526 SEQ ID NO:527                                  22 glu leu CTG 22leu1 NcoRv2 NcoRV3                                              SEQ ID NO:240 SEQ ID NO:523 SEQ ID NO:524                                     22leu4 NcoRV5 NcoRV6                                                          SEQ ID NO:241 SEQ ID NO:526 SEQ ID NO:527                                  22 glu val GTT 22val1 NcoRv2 NcoRV3                                              SEQ ID NO:242 SEQ ID NO:523 SEQ ID NO:524                                     22val4 NcoRV5 NcoRV6                                                          SEQ ID NO:243 SEQ ID NO:526 SEQ ID NO:527                                  34 leu glu GAA NcoRV1 34Glu2 NcoRV3                                              SEQ ID NO:522 SEQ ID NO:251 SEQ ID NO:524                                     NcoRV4 34Glu5 NcoRV6                                                          SEQ ID NO:525 SEQ ID NO:252 SEQ ID NO:527                                  34 leu gln CAG NcoRV1 34gln2 NcoRV3                                              SEQ ID NO:522 SEQ ID NO:248 SEQ ID NO:524                                     NcoRV4 34gln5 NcoRV5                                                          SEQ ID NO:525 SEQ ID NO:249 SEQ ID NO:527                                  34 leu thr ACC NcoRV1 34thr2 NcoRV3                                              SEQ ID NO:522 SEQ ID NO:256 SEQ ID NO:524                                     NcoRV4 34thr5 NcoRV6                                                          SEQ ID NO:525 SEQ ID NO:257 SEQ ID NO:527                                  34 leu arg CGT NcoRV1 34arg2 NcoRV3                                              SEQ ID NO:522 SEQ ID NO:246 SEQ ID NO:524                                     NcoRV4 34arg5 NcoRV6                                                          SEQ ID NO:525 SEQ ID NO:247 SEQ ID NO:527                                  34 leu ala GCT NcoRV1 34ala2 NcoRV3                                              SEQ ID NO:522 SEQ ID NO:244 SEQ ID NO:524                                     NcoRV4 34ala5 NcoRV6                                                          SEQ ID NO:525 SEQ ID NO:245 SEQ ID NO:521                                  34 leu phe TTC NcoRV1 34phe2 NcoRV3                                              SEQ ID NO:522 SEQ ID NO:254 SEQ ID NO:524                                     NcoRV4 34phe5 NcoRV6                                                          SEQ ID NO:525 SEQ ID NO:255 SEQ ID NO:527                                  34 leu ile ATC NcoRV1 34ile2 NcoRV3                                              SEQ ID NO:522 SEQ ID NO:252 SEQ ID NO:524                                     NcoRV4 34ile5 NcoRV6                                                          SEQ ID NO:525 SEQ ID NO:253 SEQ ID NO:527                                  42 gly lys AAA NcoRV1 NcoRv2 42lys3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:268                                     NcoRV4 NcoRV5 42lys6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:259                                  42 gly asn AAC NcoRV1 NcoRv2 42asn3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:260                                     NcoRV4 NaoRV5 42asn6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:261                                  42 aly thr ACC NcoRV1 NcoRv2 42thr3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:274                                     NcoRV4 NcoRV5 42thr6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:275                                  42 gly leu CTG NcoRV1 NcoRv2 42leu3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:266                                     NcoRV4 NcoRV5 42leu6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:267                                  42 gly val GTT NcoRV1 NcoRv2 42val3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:278                                     NcoRV4 NcoRV5 42val6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:279                                  42 gly glu GAA NcoRV1 NcoRv2 42glu3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:262                                     NcoRV4 NcoRV5 42glu6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:263                                  42 aly phe TTC NcoRV1 NcoRv2 42phe3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:272                                     NcoRV4 NcoRV5 42phe6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:273                                  42 aly tyr TAC NcoRV1 NcoRv2 42tyr3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:276                                     NcoRV4 NcoRV5 42tyr6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:277                                  42 gly ile ATC NcoRV1 NcoRv2 42ile3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:264                                     NcoRV4 NcoRV5 42ile6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:265                                  42 gly met ATG NcoRV1 NcoRv2 42met3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:270                                     NcoRV4 NcoRV5 42met6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:271                                  43 alu gln CAG NcoRV1 NcoRv2 43gln3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:282                                     NcoRV4 NcoRV5 43gln6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:283                                  43 glu arg CGT NcoRV1 NcoRv2 43arg3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:28O                                     NcoRV4 NcoRV5 43arg6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:281                                  43 glu thr ACC NcoRV1 NcoRv2 43thr3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:286                                     NcoRV4 NcoRV5 43thr6                                                          SEQ ED NO:525 SEQ ID NO:526 SEQ ID NO:287                                  43 glu gly GGT NcoRV1 NcoRv2 43gly3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:284                                     NcoRV4 NcoRV5 43gly6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:285                                  44 asp glu GAA NcoRV1 NcoRv2 44glu3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:294                                     NcoRV4 NcoRV5 44glu6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:265                                  44 asp asn AAC NcoRV1 NcoRv2 44asn3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:290                                     NcoRV4 NcoRV5 44asn6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:291                                  44 asp gln CAG NcoRV1 NcoRv2 44gln3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:292                                     NcoRV4 NcoRV5 44gln6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:293                                  44 asp ala GCT NcoRV1 NcoRv2 44ala3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:288                                     NcoRV4 NcoRV5 44ala6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:289                                  45 gln asp GAC NcoRV1 NcoRv2 45asp3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:332                                     NcoRV4 NcoRV5 45asp6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:303                                  45 gln asn AAC NcoRV1 NcoRv2 45asn3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:300                                     NcoRV4 NcoRV5 45asn6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:301                                  45 gln arg CGT NcoRV1 NcoRv2 45arg3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:298                                     NcoRV4 NcoRV5 45arg6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:299                                  45 gln ser TCC NcoRV1 NcoRv2 45ser3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:310                                     NcoRV4 NcoRV5 45ser6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:311                                  45 gln ala GCT NcoRV1 NcoRv2 45ala3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:296                                     NcoRV4 NcoRV5 45ala6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:297                                  45 gln ile ATC NcoRV1 NcoRv2 45ile3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:308                                     NcoRV4 NcoRV5 45ile6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:309                                  45 gln glu GAA NcoRV1 NcoRv2 45glu3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:304                                     NcoRV4 NcoRV5 45glu6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:305                                  45 gln his CAC NcoRV1 NcoRv2 45his3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:306                                     NcoRV4 NcoRV5 45his6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:307                                  46 asp glu GAA NcoRV1 NcoRv2 46glu3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:318 -    NcoRV4 NcoRV5 46glu6                                                                SEQ ID NO:525                                                             SEQ ID NO:526 SEQ                                                             ID NO:319                 46 asp asn AAC NcoRV1 NcoRv2 46asn3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:314 -    NcoRV4 NcoRV5 46asn6                                                                SEQ ID NO:525                                                             SEQ ID NO:526 SEQ                                                             ID NO:315                 46 asp gln CAG NcoRV1 NcoRv2 46gln3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:316                                     NcoRV4 NcoRV5 46gln6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:317                                  46 asp lys AAA NcoRV1 NcoRv2 46lys3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:326                                     NcoRV4 NcoRV5 46lys6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:327                                  46 asp his CAC NcoRV1 NcoRv2 46his3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:320                                     NcoRV4 NcoRV5 46his6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:321                                  46 asp ala GCT NcoRV1 NcoRv2 46ala3                                              SEQ ID NO:522 SEQ ID NO:553 SEQ ID NO:312                                     NcoRV4 NcoRV5 46ala6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:313                                  46 asp tyr TAC NcoRV1 NcoRv2 46tyr3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:329                                     NcoRV4 NcoRV5 46tyr6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:320                                  46 asp ile ATC NcoRV1 NcoRv2 46ile3                                              SEQ ID ND:522 SEQ ID NO:553 SEQ ID NO:322                                     NcoRV4 NcoRV5 46ile6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:323                                  46 asp val GTT NcoRV1 NcoRv2 46val3                                              SEQ ID NO:522 SEQ ID NO:523 SEQ ID NO:320                                     NcoRV4 NcoRV5 46val6                                                          SEQ ID NO:525 SEQ ID NO:526 SEQ ID NO:331                                  48 leu glu GAA 48glu1 RVNsi2 RVNsi3                                              SEQ ID NO:334 SEQ ID NO:526 SEQ ID NO:530                                     48glu4 RVNsi5 RVNsi6                                                          SEQ ID NO:535 SEQ ID NO:532 SEQ ID NO:533                                  48 leu lys AAA 49lys1 RVNsi2 RVNsi3                                              SEQ ID NO:336 SEQ ID NO:526 SEQ ID NO:530                                     48lys4 RVNsi5 RVNsi6                                                          SEQ ID NO:337 SEQ ID NO:532 SEQ ID NO:533                                  48 leu thr ACC 45thr1 RVNsi2 RVNsi3                                              SEQ ID NO:340 SEQ ID NO:529 SEQ ID NO:530                                     48thr4 RVNsi5 RVNsi6                                                          SEQ ID NO:341 SEQ ID NO:532 SEQ ID NO:533                                  48 leu ala GCT 48ala1 RVNsi2 RVNsi3                                              SEQ ID NO:332 SEQ ID NO:529 SEQ ID NO:530                                     48ala4 RVNsi5 RVNsi5                                                          SEQ ID NO:333 SEQ ID NO:532 SEQ ID NO:533                                  48 leu met ATG 48met1 RVNsi2 RVNsi3                                              SEQ ID NO:338 SEQ ID NO:529 SEQ ID NO:530                                     48met4 RVNsi5 RVNsi5                                                          SEQ ID NO:339 SEQ ID NO:532 SEQ ID NO:533                                  48 leu val CAC 48val1 RVNsi2 RVNsi3                                              SEQ ID NO:342 SEQ ID NO:529 SEQ ID NO:530                                     48val4 RVNsi5 RVNsi5                                                          SEQ ID NO:343 SEQ ID NO:532 SEQ ID NO:533                                  50 glu lys AAA 50lys1 RVNsi2 RVNsi3                                              SEQ ID ND:356 SEQ ID NO:529 SEQ ID NO:530                                     50lys4 RVNsi5 RVNsi6                                                          SEQ ID NO:357 SEQ ID NO:532 SEQ ID NO:533                                  50 glu asn AAC 50asn1 RVNsi2 RVNsi3                                              SEQ ID NO:352 SEQ ID NO:529 SEQ ID NO:530                                     50asn4 RVNsi5 RVNsi6                                                          SEQ ID NO:353 SEQ ID NO:532 SEQ ID NO:533                                  50 glu ser TCC 50ser1 RVNsi2 RVNsi3                                              SEQ ID NO:358 SEQ ID NO:529 SEQ ID NO:530                                     50ser4 RVNsi5 RVNsi5                                                          SEQ ID NO:359 SEQ ID NO:532 SEQ ID NO:533                                  50 glu ala GCT 50ala1 RVNsi2 RVNsi3                                              SEQ ID NO:350 SEQ ID NO:529 SEQ ID NO:530                                     50ala4 RVNsi5 RVNsi5                                                          SEQ ID NO:351 SEQ ID NO:532 SEQ ID NO:533                                  50 glu iIe ATG 50ile1 RVNsi2 RVNsi3                                              SEQ ID NO:354 SEQ ID NO:529 SEQ ID NO:530                                     50ile4 RVNsi5 RVNsi5                                                          SEQ ID NO:355 SEQ ID NO:532 SEQ ID NO:533                                  50 glu val GTT 50val1 RVNsi2 RVNsi3                                              SEQ ID NO:360 SEQ ID NO:529 SEQ ID NO:530                                     50val4 RVNsi6 RVNsi6                                                          SEQ ID NO:361 SEQ ID NO:532 SEQ ID NO:533                                  50 glu his CAC 50his1 RVNsi2 RVNsi3                                              SEQ ID NO:344 SEQ ID NO:529 SEQ ID NO:530                                     50his4 RVNsi5 RVNsi6                                                          SEQ ID NO:345 SEQ ID NO:532 SEQ ID NO:533                                  50 glu phe TTC 50phe1 RVNsi2 RVNsi3                                              SEQ ID NO:349 SEQ ID NO:529 SEQ ID NO:530                                     50phe4 RVNsi5 RVNsi6                                                          SEQ ID NO:349 SEQ ID NO:532 SEQ ID NO:533                                  50 glu met ATG 50met1 RVNsi2 RVNsi3                                              SEQ ID NO:346 SEQ ID NO:529 SEQ ID NO:530                                     50met4 RVNsi5 RVNsi6                                                          SEQ ID NO:347 SEQ ID NO:532 SEQ ID NO:533                                  54 arg asn AAC 54asn1 RVNsi2 RVNsi3                                              SEQ ID NO:364 SEQ ID NO:529 SEQ ID NO:530                                     54asn4 RVNsi5 RVNsi6                                                          SEQ ID NO:365 SEQ ID NO:532 SEQ ID NO:533                                  54 arg lys AAA 54lys1 RVNsi2 RVNsi3                                              SEQ ID NO:368 SEQ ID NO:529 SEQ ID NO:530                                     54lys4 RVNsi5 RVNsi6                                                          SEQ ID NO:369 SEQ ID NO:532 SEQ ID NO:533                                  54 arg his GAC 54his1 RVNsi2 RVNsi3                                              SEQ ID NO:366 SEQ ID NO:529 SEQ ID NO:530                                     54his4 RVNsi5 RVNsi6                                                          SEQ ID NO:367 SEQ ID NO:532 SEQ ID NO:533                                  54 arg ala GCT 54ala1 RVNsi2 RVNsi3                                              SEQ ID NO:362 SEQ ID NO:529 SEQ ID NO:530                                     54ala4 RVNsi5 RVNsi6                                                          SEQ ID NO:363 SEQ ID NO:532 SEQ ID NO:533                                  56 pro glu GAA 56glu1 RVNsi2 RVNsi3                                              SEQ ID NO:376 SEQ ID NO:529 SEQ ID NO:530                                     RVNsi4 56glu5 RVNsi6                                                          SEQ ID NO:531 SEQ ID NO:377 SEQ ID NO:533                                  56 pro gln  56gln1 RVNsi2 RVNsi3                                                 SEQ ID NO:374 SEQ ID NO:529 SEQ ID NO:530                                     RVNsi4 56gln5 RVNsi6                                                          SEQ ID NO:531 SEQ ID NO:315 SEQ ID NO:533                                  56 pro arg CGT 56arg1 RVNsi2 RVNsi3                                              SEQ ID NO:372 SEQ ID NO:529 SEQ ID NO:530                                     RVNsi4 56arg5 RVNsi6                                                          SEQ ID NO:531 SEQ ID NO:373 SEQ ID NO:533                                  56 pro his CAC 56his1 RVNsi2 RVNsi3                                              SEQ ID NO:378 SEQ ID NO:529 SEQ ID NO:530                                     RVNsi4 56his5 RVNsi6                                                          SEQ ID NO:531 SEQ ID NO:379 SEQ ID NO:533                                  56 pro thr ACC 56thr1 RVNsi2 RVNsi3                                              SEQ ID NO:384 SEQ ID NO:529 SEQ ID NO:530                                     RVNsi4 56thr5 RVNsi6                                                          SEQ ID NO:531 SEQ ID NO:365 SEQ ID NO:533                                  56 pro ala GCT 56ala1 RVNsi2 RVNsi3                                              SEQ ID NO:370 SEQ ID NO:529 SEQ ID NO:530                                     RVNsi4 56ala5 RVNsi6                                                          SEQ ID NO:531 SEQ ID NO:371 SEQ ID NO:533                                  56 pro tyr TAC 56tyr1 RVNsi2 RVNsi3                                              SEQ ID NO:386 SEQ ID NO:529 SEQ ID NO:530                                     RVNsi4 56tyr5 RVNsi6                                                          SEQ ID NO:531 SEQ ID NO:387 SEQ ID NO:533                                  56 pro phe TTC 56phe1 RVNsi2 RVNsi3                                              SEQ ID NO:382 SEQ ID NO:529 SEQ ID NO:530                                     RVNsi4 56phe5 RVNsi6                                                          SEQ ID NO:531 SEQ ID NO:383 SEQ ID NO:533                                  56 pro leu CTG 56leu1 RVNsi2 RVNsi3                                              SEQ ID NO:380 SEQ ID NO:529 SEQ ID NO:530                                     RVNsi4 56leu5 RVNsi6                                                          SEQ ID NO:531 SEQ ID NO:381 SEQ ID NO:533                                  56 pro val GTT 56val1 RVNsi2 RVNsi3                                              SEQ ID NO:388 SEQ ID NO:529 SEQ ID NO:530                                     RVNsi4 56val5 RVNsi6                                                          SEQ ID NO:531 SEQ ID NO:389 SEQ ID NO:533                                  82 leu glu GAA NsiEco1 82glu2 NsiEco3 NsiEco4                                    SEQ ID NO:534 SEQ ID NO:394 SEQ ID NO:536 SEQ ID NO:539                       NsiEco5 82glu6 NsiEco7 NsiEco8                                                SEQ ID NO:540 SEQ ID NO:395 SEQ ID NO:542 SEQ ID NO:545                    82 leu asn AAC NsiEco1 82asn2 NsiEco3 NsiEco4                                    SEQ ID NO:534 SEQ ID NO:392 SEQ ID NO:536 SEQ ID NO:539                       NsiEco5 82asn6 NsiEco7 NsiEco8                                                SEQ ID NO:540 SEQ ID NO:393 SEQ ID NO:542 SEQ ID NO:545                    82 leu his GAC NsiEco1 82his2 NsiEco8 NsiEco4                                    SEQ ID NO:534 SEQ ID NO:396 SEQ ID NO:536 SEQ ID NO:539                       NsiEco5 82his6 NsiEco7 NsiEco8                                                SEQ ID NO:540 SEQ ID NO:387 SEQ ID NO:542 SEQ ID NO:545                    82 leu thr ACC NsiEco1 82thr2 NsiEco3 NsiEco4                                    SEQ ID NO:534 SEQ ID NO:406 SEQ ID NO:536 SEQ ID NO:539                       NsiEco5 82thr6 NsiEco7 NsiEco8                                                SEQ ID NO:540 SEQ ID NO:407 SEQ ID NO:542 SEQ ID NO:545                    82 leu ser TCC NsiEco1 82ser2 NsiEco8 NsiEco4                                    SEQ ID NO:534 SEQ ID NO:404 SEQ ID NO:536 SEQ ID NO:539                       NsiEco5 82ser6 NsiEco7 NsiEco8                                                SEQ ID NO:540 SEQ ID NO:405 SEQ ID NO:542 SEQ ID NO:545                    82 leu ala GCT NsiEco1 82ala2 NsiEco3 NsiEco4                                    SEQ ID NO:534 SEQ ID NO:390 SEQ ID NO:536 SEQ ID NO:539                       NsiEco5 92ala6 NsiEco7 NsiEco8                                                SEQ ID NO:540 SEQ ID NO:391 SEQ ID NO:542 SEQ ID NO:545                    92 leu tyr TAC NsiEco1 92tyr2 NsiEco3 NsiEco4                                    SEQ ID NO:534 SEQ ID NO:408 SEQ ID NO:536 SEQ ID NO:539                       NsiEco5 82tyr6 NsiEco7 NsiEco8                                                SEQ ID NO:540 SEQ ID NO:409 SEQ ID NO:542 SEQ ID NO:545                    82 leu phe TTC NsiEco1 82phe2 NsiEco3 NsiEco4                                    SEQ ID NO:534 SEQ ID NO:402 SEQ ID NO:536 SEQ ID NO:539                       NsiEco5 82phe6 NsiEco7 NsiEco8                                                SEQ ID NO:540 SEQ ID NO:403 SEQ ID NO:542 SEQ ID NO:545                    82 leu ile ATC NsiEco1 92ile2 NsiEco3 NsiEco4                                    SEQ ID NO:534 SEQ ID NO:338 SEQ ID NO:539 SEQ ID NO:539                       NsiEco5 92ile6 NsiEco7 NsiEco8                                                SEQ ID NO:540 SEQ ID NO:399 SEQ ID NO:542 SEQ ID NO:545                    82 leu met ATG NsiEco1 92met2 NsiEco3 NsiEco4                                    SEQ ID NO:534 SEQ ID NO:400 SEQ ID NO:536 SEQ ID NO:539                       NsiEco5 82met6 NsiEco7 NsiEco8                                                SEQ ID NO:540 SEQ ID NO:401 SEQ ID NO:542 SEQ ID NO:545                    92 pro ala GCT NsiEco1 NsiEco2 92ala3A NsiEco3B NsiEco4                          SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:410 SEQ ID NO:536 SEQ ID                                                                 NO:539                       NsiEco5 NsiEco6 NsiEco7A 92ala7B NsiEco8                                      SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:543 SEQ ID NO:411 SEQ ID                                                                 NO:545                    92 pro gly GGT NsiEco1 NsiEco2 92gly3A NsiEco3B NsiEco4                          SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:412 SEQ ID NO:538 SEQ ID                                                                 NO:539                       NsiEco5 NsiEco6 NsiEco7A 92ala7B NsiEco8                                      SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:543 SEQ ID NO:415 SEQ ID                                                                 NO:545                    92 pro ile ATC NsiEco1 NsiEco2 92ile3A NsiEco3B NsiEco4                          SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:414 SEQ ID NO:538 SEQ ID                                                                 NO:539                       NsiEco5 NsiEco6 NsiEco7A 92ala7B NsiEco8                                      SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:543 SEQ ID NO:415 SEQ ID                                                                 NO:545                    94 arg gln CAG NsiEco1 NsiEco2 NsiEco3A 94gln3B NsiEco4                          SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:537 SEQ ID NO:418 SEQ ID                                                                 NO:539                       NsiEco5 NsiEco6 NsiEco7A 94gln7B NsiEco8                                      SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:543 SEQ ID NO:419 SEQ ID                                                                 NO:545                    94 arg lys AAA NsiEco1 NsiEco2 NsiEco3A 94lys3B NsiEco4                          SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:537 SEQ ID NO:422 SEQ ID                                                                 NO:539                       NsiEco5 NsiEco6 NsiEco7A 94lys7B NsiEco8                                      SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:543 SEQ ID NO:423 SEQ ID                                                                 NO:545                    94 arg his CAC NsiEco1 NsiEco2 NsiEco3A 94his3B NsiEco4                          SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:537 SEQ ID NO:420 SEQ ID                                                                 NO:539                       NsiEco5 NsiEco6 NsiEco7A 94his7B NsiEco8                                      SEQ ID NO:540 SEQ ID NO:536 SEQ ID NO:443 SEQ ID NO:421 SEQ ID                                                                 NO:545                    94 arg ala GCT NsiEco1 NsiEco2 NsiEo3A 94ala3B NsiEco4                           SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:537 SEQ ID NO:416 SEQ ID                                                                 NO:539                       NsiEco5 NsiEco6 NsiEco7A 94ala7B NsiEco8                                      SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:543 SEQ ID NO:417 SEQ ID                                                                 NO:545                    95 his asn AAC NsiEco1 NsiEco2 NsiEco3A 95asn3B NsiEco4                          SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:537 SEQ ID NO:426 SEQ ID                                                                 NO:539                       NsiEco5 NsIEco6 NsiEco7A 95asn7B NsiEco8                                      SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:543 SEQ ID NO:427 SEQ ID                                                                 NO:545                    95 his lys AAA NsiEco1 NsiEco2 NsiEco3A 95lys3B NsiEco4                          SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:537 SEQ ID NO:432 SEQ ID                                                                 NO:539                       NsiEco5 NsiEco6 NsiEco7A 95lys7B NsiEco8                                      SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:543 SEQ ID NO:433 SEQ ID                                                                 NO:545                    95 his ser TCC NsiEco1 NsiEco2 NsiEco3A 95ser3B NsiEco4                          SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:537 SEQ ID NO:438 SEQ ID                                                                 NO:539                       NsiEco5 NsiEc06 NsiEco7A 95ser7B NsiEco8                                      SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:543 SEQ ID NO:439 SEQ ID                                                                 NO:545                    95 his ala GCT NsiEco1 NsiEco2 NsiEco3A 95ala3B NsiEco4                          SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:537 SEQ ID NO:424 SEQ ID                                                                 NO:539                       NsiEco5 NsiEco6 NsiEco7A 95ala7B NsiEco8                                      SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:543 SEQ ID NO:425 SEQ ID                                                                 NO:545                    95 his trp TGG NsiEco1 NsiEco2 NsiEco3A 95trp3B NsiEco4                          SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:537 SEQ ID NO:440 SEQ ID                                                                 NO:539                       NsiEco5 NsiEco6 NsiEco7A 95trp7B NsiEco8                                      SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:543 SEQ ID NO:441 SEQ ID                                                                 NO:545                    95 his phe TTC NsiEco1 NsiEco2 NsiEco3A 95phe3B NsiEco4                          SEQ ID NO:534 SEQ ID NO:555 SEQ ID NO:537 SEQ ID NO:11 SEQ ID NO:539          NsiEco5 NsiEco6 NsiEco7A 95phe7B NsiEco8                                      SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:543 SEQ ID NO:437 SEQ ID                                                                 NO:545                    95 his ile ATC NsiEco1 NsiEco2 NsiEco3A 96ile3B NsiEco4                          SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:537 SEQ ID NO:430 SEQ ID                                                                 NO:539                       NsiEco5 NsiEco6 NsiEco7A 98ile7B NsiEco8                                      SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:543 SEQ ID NO:431 SEQ ID                                                                 NO:545                    98 his glu GAA NsiEco1 NsiEco2 NsiEco3A 98glu3B NsiEco4                          SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:537 SEQ ID NO:446 SEQ ID                                                                 NO:539                       NsiEco5 NsiEco6 NsiEco7A 98glu7B NsiEco8                                      SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:543 SEQ ID NO:447 SEQ ID                                                                 NO:545                    98 his gln CAA NsiEco1 NsEco2 NsiECo3A 98gln3B NsiEco4                           SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:537 SEQ ID NO:444 SEQ ID                                                                 NO:539                       NsiEco5 NsiEco6 NsiEco7A 98gln7B NsiEco8                                      SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:543 SEQ ID NO:445 SEQ ID                                                                 NO:545                    98 his ser TCC NsiEco1 NsiEco2 NsiEco3A 98ser3B NsiEcor                          SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:537 SEQ ID NO:452 SEQ ID                                                                 NO:539                       NsiEco5 NsiEco6 NsiEco7A 98ser7B NsiEco8                                      SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:543 SEQ ID NO:453 SEQ ID                                                                 NO:545                    98 his phe TTC NsiEco1 NsiEco2 NsiEco3A 98phe3B NsiEco4                          SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:537 SEQ ID NO:450 SEQ ID                                                                 NO:539                       NsiEco5 NsiEco6 NsiEco7A 98phe7B NsiEco8                                      SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:543 SEQ ID NO:451 SEQ ID                                                                 NO:545                    98 his met ATG NsiEco1 NsiEco2 NsiEco3A 98met3B NsiEco4                          SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:537 SEQ ID NO:448 SEQ ID                                                                 NO:539                       NsiEco5 NsiEco6 NsiEco7A 98met7B NsiEco8                                      SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:543 SEQ ID NO:449 SEQ ID                                                                 NO:545                    98 his val GTA NsiEco1 NsiEco2 NsiEco3A 98val3B NsiEco4                          SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:537 SEQ ID NO:454 SEQ ID                                                                 NO:539                       NsiEco5 NsiEco6 NsiEco7A 98val7B NsiEco8                                      SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:543 SEQ ID NO:455 SEQ ID                                                                 NO:545                    98 Ns lys AAA NsiEco1 NsiEco2 NsiEco3A 98lys3B NsiEco4                           SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:537 SEQ ID NO:458 SEQ ID                                                                 NO:539                       NsiEco5 NsiEco6 NsiEco7A 98lys7B NsiEc08                                      SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:543 SEQ ID NO:459 SEQ ID                                                                 NO:545                    98 his arg CGT NsiEco1 NsiEco2 NsiEco3A 98arg3B NsiEco4                          SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:537 SEQ ID NO:456 SEQ ID                                                                 NO:539                       NsiEco5 NsiEco6 NsiEco7A 98arg76 NsiEco8                                      SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:543 SEQ ID NO:457 SEQ ID                                                                 NO:545                    98 his tyr TAC NsiEco1 NsiEco2 NsiEco3A 98tyr3B NsiEco4                          SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:537 SEQ ID NO:60 SEQ ID NO:539          NsiEco5 NsiEco6 NsiEco7A 98tyr7B NsiEco8                                      SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:543 SEQ ID NO:461 SEQ ID                                                                 NO:545                    101 asp glu GAA NsiEco1 NsiEco2 NsiEco3 101glu4                                  SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:535 SEQ ID NO:466                       NsiEco5 NsiEco6 NsiEco7 101glu8                                               SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:542 SEQ ID NO:467                    101 asp asn AAC NsiEco1 NsiEco2 NsiEco3 101asn4                                  SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:538 SEQ ID NO:464                       NsiEco5 NsiEco6 NsiEco7 101asn8                                               SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:542 SEQ ID NO:465                    101 asp ser TCC NsiEco1 NsiEco2 NsiEco3 101ser4                                  SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:536 SEQ ID NO:476                       NsiEco5 NsiEc06 NsiEco7 101ser8                                               SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:542 SEQ ID NO:477                    101 asp ala GCT NsiEco1 NsiEco2 NsiEco3 101ala4                                  SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:538 SEQ ID NO:462                       NsiEco5 NsiEco6 NsiEco7 101ala8                                               SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:542 SEQ ID NO:463                    101 asp gly GGT NsiEco1 NsiEco2 NsiEco3 101gly4                                  SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:536 SEQ ID NO:468                       NsiEco5 NsiEco6 NsiEco7 101gly8                                               SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:542 SEQ ID NO:469                    101 asp ile ATC NsiEco1 NsiEco2 NsiEco3 101ile4                                  SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:536 SEQ ID NO:470                       NsiEco5 NsIEco6 NsiEco7 101ile8                                               SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:542 SEQ ID NO:471                    101 asp leu CTG NsiEco1 NsiEco2 NsiEco3 101leu4                                  SEQ ID NO:534 SEQ ID NO:535 SEQ ID NO:536 SEQ ID NO:472                       NsiEco5 NsiEco6 NsiEco7 101leu8                                               SEQ ID NO:540 SEQ ID NO:541 SEQ ID NO:542 SEQ ID NO:473                    108 arg gln CAG 108gln1 EcoHin2                                                  SEQ ID NO:480 SEQ ID NO:547                                                   108gln3 EcoHin4                                                               SEQ ID NO:481 SEQ ID NO:549                                                108 arg his CAC 108his1 EcoHin2                                                  SEQ ID NO:482 SEQ ID NO:547                                                   108his3 EcoHin4                                                               SEQ ID NO:483 SEQ ID NO:549                                                108 arg ser TCC 108ser1 EcoHin2                                                  SEQ ID NO:484 SEQ ID NO:547                                                   108ser3 EcoHin4                                                               SEQ ID NO:485 SEQ ID NO:549                                                108 arg ala GCT 108ala1 EcoHin2                                                  SEQ ID NO:478 SEQ ID NO:547                                                   108ala3 EcoHin4                                                               SEQ ID NO:479 SEQ ID NO:549                                                110 lys arg CGT 110arg1 EcoHin2                                                  SEQ ID NO:486 SEQ ID NO:547                                                   110arg3 EcoHin4                                                               SEQ ID NO:487 SEQ ID NO:549                                                110 lys his CAC 110his1 EcoHin2                                                  SEQ ID NO:490 SEQ ID NO:547                                                   110his3 EcoHin4                                                               SEQ ID NO:491 SEQ ID NO:549                                                110 lys glu GAA 110glu1 EcoHin2                                                  SEQ ID NO:488 SEQ lD NO:547                                                   110glu3 EcoHin4                                                               SEQ ID NO:489 SEQ ID NO:549                                                110 lys ser TCC 110ser1 EcoHin2                                                  SEQ ID NO:494 SEQ ID NO:547                                                   110ser3 EcoHin4                                                               SEQ ID NO:495 SEQ ID NO:549                                                110 lys ala GCT 110ala1 EcoHin2                                                  SEQ ID NO:492 SEQ ID NO:547                                                   110ala3 EcoHin4                                                               SEQ ID NO:493 SEQ ID NO:549                                                113 phe asp GAC 113asp1 EcoHin2                                                  SEQ ID NO:495 SEQ ID NO:547                                                   113asp3 EcoHin4                                                               SEQ ID NO:497 SEQ ID NO:549                                                113 phe lys AAA 113lys1 EcoHin2                                                  SEQ ID NO:502 SEQ lD NO:547                                                   113lys3 EcoHin4                                                               SEQ ID NO:503 SEQ ID NO:549                                                113 phe leu CTG 113leu1 EcoHin2                                                  SEQ ID NO:500 SEQ ID NO:547                                                   113leu3 EcoHin4                                                               SEQ ID NO:501 SEQ ID NO:549                                                113 phe ile ATC 113ile1 EcoHin2                                                  SEQ ID NO:499 SEQ ID NO:547                                                   113ile3 EcoHin4                                                               SEQ ID NO:499 SEQ ID NO:549                                                113 phe val GTT 113val1 EcoHin2                                                  SEQ ID NO:504 SEQ ID NO:547                                                   113val3 EcoHin4                                                               SEQ ID NO:505 SEQ ID NO:549                                                116 lys asn AAC 116asn1 EcoHin2                                                  SEQ ID NO:510 SEQ lD NO:547                                                   116asn3 EcoHin4                                                               SEQ ID NO:511 SEQ ID NO:549                                                116 lys arg CGT 116ara1 EcoHin2                                                  SEQ ID NO:509 SEQ ID NO:547                                                   116arg3 EcoHin4                                                               SEQ ID NO:509 SEQ ID NO:549                                                116 lys his CAC 116his1 EcoHin2                                                  SEQ ID NO:514 SEQ ID NO:547                                                   116his3 EcoHin4                                                               SEQ ID NO:515 SEQ ID NO:549                                                116 lys ala GCT 116ala1 EcoHin2                                                  SEQ ID NO:506 SEQ ID NO:547                                                   116ala3 EcoHin4                                                               SEQ ID NO:507 SEQ ID NO:549                                                116 lys tyr TAC 116tyr1 EcoHin2                                                  SEQ ID NO:520 SEQ ID NO:547                                                   116tyr3 EcoHin4                                                               SEQ ID NO:521 SEQ ID NO:549                                                116 lys phe TTC 116phe1 EcoHin2                                                  SEQ ID NO:518 SEQ ID NO:547                                                   116phe3 EcoHin4                                                               SEQ ID NO:519 SEQ ID NO:549                                                116 lys gln CAG 116gln1 EcoHin2                                                  SEQ ID NO:512 SEQ ID NO:547                                                   116gln3 EcoHin4                                                               SEQ ID NO:513 SEQ ID NO:549                                                116 lys met ATG 116met1 EcoHin2                                                  SEQ ID NO:516 SEQ ID NO:547                                                   116met3 EcoHin4                                                               SEQ ID NO:517 SEQ ID NO:549                                              __________________________________________________________________________                                position/native a.a.                                                                   substitution                                                                        codon                                                                             parental plasmid                                                                      restriction            __________________________________________________________________________                                                           digest                   21 asp glu GAA pMON13356 NcoI, EcoRV                                          21 asp gln CAA pMON13356 NcoI, EcoRV                                          21 asp asn AAC pMON13356 NcoI, EcoRV                                          21 asp thr ACC pMON13356 NcoI, EcoRV                                          21 asp ser AGC pMON13356 NcoI, EcoRV                                          22 glu asp GAC pMON13356 NcoI, EcoRV                                          22 glu asn AAC pMON13356 NcoI, EcoRV                                          22 glu gln CAG pMON13356 NcoI, EcoRV                                          22 glu leu CTG pMON13356 NcoI, EcoRV                                          22 glu val GTT pMON13356 NcoI, EcoRV                                          34 leu glu GAA pMON13356 NcoI, EcoRV                                          34 leu gln CAG pMON13356 NcoI, EcoRV                                          34 leu thr ACC pMON13356 NcoI, EcoRV                                          34 leu arg CGT pMON13356 NcoI, EcoRV                                          34 leu ala GCT pMON13356 NcoI, EcoRV                                          34 leu phe TTC pMON13356 NcoI, EcoRV                                          34 leu ile ATC pMON13356 NcoI, EcoRV                                          42 gly asn AAC pMON13356 NcoI, EcoRV                                          42 gly thr ACC pMON13356 NcoI, EcoRV                                          42 gly leu CTG pMON13356 NcoI, EcoRV                                          42 gly val GTT pMON13356 NcoI, EcoRV                                          42 gly glu GAA pMON13356 NcoI, EcoRV                                          42 gly phe TTC pMON13356 NcoI, EcoRV                                          42 gly tyr TAC pMON13356 NcoI, EcoRV                                          42 gly ile ATC pMON13356 NcoI, EcoRV                                          42 gly met ATG pMON13356 NcoI, EcoRV                                          43 glu gln CAG pMON13356 NcoI, EcoRV                                          43 glu arg CGT pMON13356 NcoI, EcoRV                                          43 glu thr ACC pMON13356 NcoI, EcoRV                                          43 glu gly GGT pMON13356 NcoI, EcoRV                                          44 asp glu GAA pMON13356 NcoI, EcoRV                                          44 asp asn AAC pMON13356 NcoI, EcoRV                                          44 asp gln CAG pMON13356 NcoI, EcoRV                                          44 asp ala GCT pMON13356 NcoI, EcoRV                                          45 gln asp GAC pMON13356 NcoI, EcoRV                                          45 gln asn AAC pMON13356 NcoI, EcoRV                                          45 gln arg CGT pMON13356 NcoI, EcoRV                                          45 gln ser TCC pMON13356 NcoI, EcoRV                                          45 gln ala GCT pMON13356 NcoI, EcoRV                                          45 gln ile ATC pMON13356 NcoI, EcoRV                                          45 gln glu GAA pMON13356 NcoI, EcoRV                                          45 gln his CAC pMON13356 NcoI, EcoRV                                          46 asp glu GAA pMON13356 NcoI, EcoRV                                          46 asp asn AAC pMON13356 NcoI, EcoRV                                          46 asp gln CAG pMON13356 NcoI, EcoRV                                          46 asp lys AAA pMON13356 NcoI, EcoRV                                          46 asp his CAC pMON13356 NcoI, EcoRV                                          46 asp ala GCT pMON13356 NcoI, EcoRV                                          46 asp tyr TAC pMON13356 NcoI, EcoRV                                          46 asp ile ATC pMON13356 NcoI, EcoRV                                          46 asp val GTT pMON13356 NcoI, EcoRV                                          48 leu glu GAA pMON13357 EcoRV, NcoI                                          48 leu lys AAA pMON13357 EcoRV, NcoI                                          48 leu thr ACC pMON13357 EcoRV, NcoI                                          48 leu ala GCT pMON13357 EcoRV, NcoI                                          48 leu met ATG pMON13357 EcoRV, NcoI                                          48 leu val CAC pMON13357 EcoRV, NcoI                                          50 glu lys AAA pMON13357 EcoRV, NcoI                                          50 glu asn AAC pMON13357 EcoRV, NcoI                                          50 glu ser TCC pMON13357 EcoRV, NcoI                                          50 glu ala GCT pMON13357 EcoRV, NcoI                                          50 glu ile ATC pMON13357 EcoRV, NcoI                                          50 glu val GTT pMON13357 EcoRV, NcoI                                          50 glu his CAC pMON13357 EcoRV, NcoI                                          50 glu phe TTC pMON13357 EcoRV, NcoI                                          50 glu met ATG pMON13357 EcoRV, NcoI                                          54 arg asn AAC pMON13357 EcoRV, NcoI                                          54 arg lys AAA pMON13357 EcoRV, NcoI                                          54 arg his CAC pMON13357 EcoRV, NcoI                                          54 arg ala GCT pMON13357 EcoRV, NcoI                                          56 pro glu GAA pMON13357 EcoRV, NcoI                                          56 pro gln  pMON13357 EcoRV, NcoI                                             56 pro arg CGT pMON13357 EcoRV, NcoI                                          56 pro his CAC pMON13357 EcoRV, NcoI                                          56 pro thr ACC pMON13357 EcoRV, NcoI                                          56 pro ala GCT pMON13357 EcoRV, NcoI                                          56 pro tyr TAC pMON13357 EcoRV, NcoI                                          56 pro phe TTC pMON13357 EcoRV, NcoI                                          56 pro leu CTG pMON13357 EcoRV, NcoI                                          56 pro val GTT pMON13357 EcoRV, NcoI                                          82 leu glu GAA pMON13358 NsiI, EcoRI                                          82 leu asn AAC pMON13358 NsiI, EcoRI                                          82 leu his CAC pMON13358 NsiI, EcoRI                                          82 leu thr ACC pMON13358 NsiI, EcoRI                                          82 leu ser TCC pMON13358 NsiI, EcoRI                                          82 leu ala GCT pMON13358 NsiI, EcoRI                                          82 leu tyr TAC pMON13358 NsiI, EcoRI                                          82 leu phe TTC pMON13358 NsiI, EcoRI                                          82 leu ile ATC pMON13358 NsiI, EcoRI                                          82 leu met ATG pMON13358 NsiI, EcoRI                                          92 pro ala GCT pMON13358 NsiI, EcoRI                                          92 pro gly GGT pMON13358 NsiI, EcoRI                                          92 pro ile ATC pMON13358 NsiI, EcoRI                                          94 arg gln CAG pMON13358 NsiI, EcoRI                                          94 arg lys AAA pMON13358 NsiI, EcoRI                                          94 arg his CAC pMON13358 NsiI, EcoRI                                          94 arg ala GCT pMON13358 NsiI, EcoRI                                          95 his asn AAC pMON13358 NsiI, EcoRI                                          95 his lys AAA pMON13358 NsiI, EcoRI                                          95 his ser TCC pMON13358 NsiI, EcoRI                                          95 his ala GCT pMON13358 NsiI, EcoRI                                          95 his trp TGG pMON13358 NsiI, EcoRI                                          95 his phe TTC pMON13358 NsiI, EcoRI                                          95 his ile ATC pMON13358 NsiI, EcoRI                                          98 his glu GAA pMON13358 NsiI, EcoRI                                          98 his gln CAA pMON13358 NsiI, EcoRI                                          98 his ser TCC pMON13358 NsiI, EcoRI                                          98 his phe TTC pMON13358 NsiI, EcoRI                                          98 his met ATG pMON13358 NsiI, EcoRI                                          98 his val GTA pMON13358 NsiI, EcoRI                                          98 his lys AAA pMON13358 NsiI, EcoRI                                          98 his arg CGT pMON13358 NsiI, EcoRI                                          98 his tyr TAC pMON13358 NsiI, EcoRI                                          101 asp glu GAA pMON13358 NsiI, EcoRI                                         101 asp asn AAC pMON13358 NsiI, EcoRI                                         101 asp ser TCC pMON13358 NsiI, EcoRI                                         101 asp ala GCT pMON13358 NsiI, EcoRI                                         101 asp gly GGT pMON13358 NsiI, EcoRI                                         101 asp ile ATC pMON13358 NsiI, EcoRI                                         101 asp leu CTG pMON13358 NsiI, EcoRI                                         108 arg gln CAG pMON13359 EcoRI, HinDIII                                      108 arg his CAC pMON13359 EcoRI, HinDIII                                      108 arg ser TCC pMON13359 EcoRI, HinDIII                                      108 arg ala GCT pMON13359 EcoRI, HinDIII                                      110 lys arg CGT pMON13359 EcoRI, HinDIII                                      110 lys his CAC pMON13359 EcoRI, HinDIII                                      110 lys glu GAA pMON13359 EcoRI, HinDIII                                      110 lys ser TCC pMON13359 EcoRI, HinDIII                                      110 lys ala GCT pMON13359 EcoRI, HinDIII                                      113 phe asp GAC pMON13359 EcoRI, HinDIII                                      113 phe lys AAA pMON13359 EcoRI, HinDIII                                      113 phe leu CTG pMON13359 EcoRI, HinDIII                                      113 phe leu CTG pMON13359 EcoRI, HinDIII                                      113 phe ile ATC pMON13359 EcoRI, HinDIII                                      113 phe Val GTT pMON13359 EcoRI, HinDIII                                      116 lys asn AAC pMON13359 EcoRI, HinDIII                                      116 lys arg CGT pMON13359 EcoRI, HinDIII                                      116 lys his CAC pMON13359 EcoRI, HinDIII                                      116 lys ala GCT pMON13359 EcoRI, HinDIII                                      116 lys tyr TAC pMON13359 EcoRI, HinDIII                                      116 lys phe TTC pMON13359 EcoRI, HinDIII                                      116 lys gln CAG pMON13359 EcoRI, HinDIII                                      116 lys met ATG pMON13359 EcoRI, HinDIII                                    __________________________________________________________________________

It will be apparent to those skilled in the art that other codonsbesides those shown in Table 8 can also code for the substituted aminoacids in the hIL-3 muteins. The present invention includes the DNAsencoding the mutant hIL-3 polypeptides in the invention including thevarious codons which can code for the parental and substituted aminoacids of the hIL-3 muteins of the invention due to the degeneracy of thegenetic code.

hIL-3 (15-125) variant genes encoding the variants listed in Table 8 canalso be expressed from intracellular expression vectors to produce largequantities of the variant protein which can be purified and assayed forbiological activity. The hIL-3 variant genes, from Table 8, can beexcised from the secretion expression vector, as a 345 base pairNcoI/HindIII fragment and ligated into an appropriate intrecellularexpression vector, such as pMON2341 digested with NcoI and HindIII.

Table 9 shows the biological activity of (15-125) hIL-3 muteins of thepresent invention which have one amino acid substitutions in the(15-125) hIL-3 polypeptide and which were constructed as described inExample 66. The mutants in Table 9 were secreted into the periplasmicspace in E. coli. The periplasmic content was released by osmotic shockand the material in the crude osmotic shock fraction was screened forgrowth promoting activity. Biological activity is the growth promotingactivity of AML cells relative to (15-125) hIL-3 (pMON6458 orpMMON5988). The relative biological activity of IL-3 mutants iscalculated by dividing the EC₅₀ (1-133) hIL-3 by the EC₅₀ of the mutant.The numbers in parentheses indicate the number of repeat assays. When avariant was assayed more than once the standard deviation is indicated.An "*" indicates that the hIL3 variant protein level was less than 1.0μg/ml and was not screened for growth promoting activity.

                  TABLE 9                                                         ______________________________________                                                      (15-125) hIL-3 MUTANT                                           PARENTAL                             BIOL                                     aa position                                                                          AA     codon   AA   SEQ ID NO:                                                                            codon ACTIVITY                             ______________________________________                                        21/7   ASP    GAT     ASN  19      AAC   0.01                                   21/7 ASP GAT GLN 19 CAA 0.07                                                  21/7 ASP GAT GLU 19 GAA 0.5                                                   21/7 ASP GAT SER 19 AGC 0.1                                                   21/7 ASP GAT THR 19 ACC 0.1                                                   22/8 GLU GAA ASN 19 AAC *                                                     22/8 GLU GAA ASP 19 GAC *                                                     22/8 GLU GAA GLN 19 CAG <0.01                                                 22/8 GLU GAA LEU 19 CTG *                                                     22/8 GLU GAA VAL 19 GTT *                                                     34/20 LEU TTG ALA 19 GLT 2.2                                                  34/20 LEU TTG ARG 19 CGT 2.2                                                  34/20 LEU TTG GLN 19 CAG 1.1                                                  34/20 LEU TTG GLU 19 GAA 1.5                                                  34/20 LEU TTG ILE 19 ATC 1.3                                                  34/20 LEU TTG PHE 19 TTC 1.8                                                  34/20 LEU TTG ILE 19 ACC 1.l                                                  42/28 GLY GGG ASN 19 AAC 1.3 (3) 0.28                                         42/28 GLY GGG ILE 19 ATC 10                                                   42/28 GLY GGG LEU 19 CTG 10.1 (3) 7.57                                        42/28 GLY GGG MET 19 ATG 2.2 (3) 1.14                                         42/28 GLY GGG THR 19 TAC 11 (2) 8.9                                           42/28 GLY GGG VAL 19 GTT 0.33                                                 43/29 GLU GAA AAG 19 CGT *                                                    43/29 GLU GAA GLN 19 CAG <0.004                                               43/29 GLU GAA GLY 19 GGT *                                                    43/29 GLU GAA ILE 19 ACC 0.005                                                44/30 ASP GAC ALA 19 GCT *                                                    44/30 ASP GAC ASN 19 AAC *                                                    44/30 ASP GAC GLN 19 CAG *                                                    44/30 ASP GAC GLU 19 GAA 0.66                                                 45/31 GLN CAA ALA 19 GCT 1                                                    45/31 GLN CAA ASN 19 AAC 15.8                                                 45/31 GLN CAA GLU 19 GAA 2.3                                                  45/31 GLN CAA ILE 19 ATC 4.9                                                  45/31 GLN CAA SER 19 TCC 0.7                                                  46/32 ASP GAC ALA 19 GCT 6.3                                                  46/32 ASP GAC ASN 19 AAC 0.66, 1.1                                            46/32 ASP GAC GLN 19 CAG 6.3                                                  46/32 ASP GAC GLU 19 GAA 1.97 (3) 2.14                                        46/32 ASP GAC HIS 19 CAC 3.2, 1.4                                             46/32 ASP GAC ILE 19 ATC 0.5                                                  46/32 ASP GAC LYS 19 AAA 0.5                                                  46/32 ASP GAC TYR 19 TAC 0.66                                                 46/32 ASP GAC VAL 19 GTT 6.3                                                  48/34 LEU CTG GLU 19 GAA *                                                    48/34 LEU CTG HIS 19  *                                                       48/34 LEU CTG LYS 19 AAA *                                                    48/34 LEU CTG THR 19 ACC *                                                    48/34 LEU CTG VAL 19 CAC *                                                    50/36 GLU GAA ALA 19 GCT 0.5                                                  50/36 GLU GAA ASN 19 AAC 1.7                                                  50/36 GLU GAA HIS 19 CAC *                                                    50/36 GLU GAA LYS 19 AAA *                                                    50/36 GLU GAA TYR 19 TAC 1.3                                                  50/36 GLU GAA VAL 19 GTT *                                                    54/40 ARG CGA ALA 19 GCT 0.9                                                  54/40 ARG CGA ASN 19 AAC *                                                    54/40 ARG CGA HIS 19 CAC 0.01                                                 54/40 ARG CGA LYS 19 AAA 0.2                                                  56/42 PRO CAA ALA 19 GCT 1.8                                                  56/42 PRO CAA ASN 19  0.6                                                     56/42 PRO CAA ARG 19 CGT 1.2                                                  56/42 PRO CAA GLU 19 GAA 0.9                                                  56/42 PRO CAA HIS 19 CAC 0.4                                                  56/42 PRO CAA LEU 19 CTG 1.2                                                  56/42 PRO CAA PHE 19 TTC                                                      56/42 PRO CAA THR 19 ACC 0.6                                                  56/42 PRO CAA VAL 19 GTT 1.1                                                  82/68 LEU CTG ALA 19 GCT 0.5                                                  82/68 LEU GTG ASN 19 AAC 2.9                                                  82/68 LEU CTG GLU 19 GAA 4.57 (3) 5.0                                         82/68 LEU CTG HlS 19 CAC 2.2                                                  82/68 LEU CTG ILE 19 ATC 0.8                                                  82/68 LEU CTG MET 19 ATG 1.1                                                  82/68 LEU CTG PHE 19 TTC 3.2                                                  82/68 LEU CTG SER 19 TCC 2.2                                                  82/68 LEU CTG THR 19 ACC 1.6                                                  82/68 LEU CTG TYR 19 TAC 2.7                                                  94/80 ARG CGA GLN 19 CAG 0.03                                                 94/80 ARG CGA HIS 19 CAC 0.01                                                 94/80 ARG CGA LYS 19 AAA *                                                    95/81 HIS CAT ASN 19 AAC 2.7 (2) 2.3                                          95/81 HIS CAT ILE 19 ATC 0.33                                                 95/81 HIS CAT LYS 19 AAA 0.9                                                  95/81 HIS CAT MET 19 ATG 1                                                    95/81 HIS CAT ILE 19 TTC 0.66                                                 95/81 HIS CAT SER 19 TCC 4                                                    95/81 HIS CAT TRP 19 TGG *                                                    98/84 HIS CAT ARG 19 CGT 3.2                                                  98/84 HIS CAT GLN 19 CAA 2.2                                                  98/84 HIS CAT GLU 19 GAA 1.55 (2) 0.15                                        98/84 HIS CAT LYS 19 AAA 4                                                    98/84 HIS CAT MET 19 ATG 2.2                                                  98/84 HIS CAT PHE 19 TTC 1                                                    98/84 HIS CAT SER 19 TCC 4                                                    98/84 HIS CAT THR 19  2.2                                                     98/84 HIS CAT VAL 19 GTA 2.4 (2) 0.8                                          101/87 ASP GAC ASN 19 AAC 7                                                   101/87 ASP GAC GLU 19 GAA *                                                   101/87 ASP GAC ILE 19 ATC 3.2                                                 101/87 ASP GAC LEU 19 CTG 3.2                                                 108/94 ARG CGG ALA 19 GCT 4                                                   108/94 ARG CGG GLN 19 CAG 0.4                                                 108/94 ARG CGG HIS 19 CAC *                                                   108/94 ARG CGG SER 19 TCC 3.7                                                 110/96 LYS AAA GLU 19 GAA *                                                   110/96 LYS AAA HIS 19 CAC *                                                   110/96 LYS AAA ILE 19 ATC *                                                   113/99 PHE TTC ASP 19 GAC *                                                   113/99 PHE TTC ILE 19 ATC *                                                   113/99 PHE TTC LEU 19 CTG *                                                   113/99 PHE TTC LYS 19 AAA *                                                   116/102 LYS AAA ALA 19 GCT 5                                                  116/102 LYS AAA ARG 19 CGT 0.03                                               116/102 LYS AAA ASN 19 AAC 0.22                                               116/102 LYS AAA GLN 19 CAG 0.33                                               116/102 LYS AAA HIS 19 CAC 3.2                                                116/102 LYS AAA MET 19 ATG 0.9                                                116/102 LYS AAA PHE 19 TTC 2.5                                                116/102 LYS AAA TYR 19 TAC 5.4 (2) 0.3                                      ______________________________________                                    

    __________________________________________________________________________    #             SEQUENCE LISTING                                                   - -  - - (1) GENERAL INFORMATION:                                             - -    (iii) NUMBER OF SEQUENCES: 549                                         - -  - - (2) INFORMATION FOR SEQ ID NO:1:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 23 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:1:                        - - CTAGCGATCT TTTAATAAGC TTG           - #                  - #                    23                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:2:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 23 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:2:                        - - GATCCAAGCT TATTAAAAGA TCG           - #                  - #                    23                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:3:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 69 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:3:                        - - GGCAACAATT TCTACAAAAC ACTTGATACT GTATGAGCAT ACAGTATAAT TG -             #CTTCAACA     60                                                                 - - GAACAGATC                - #                  - #                      - #         69                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:4:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 67 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:4:                        - - TGTTCTGTTG AAGCAATTAT ACTGTATGCT CATACAGTAT CAAGTGTTTT GT -             #AGAAATTG     60                                                                 - - TTGCCGC                 - #                  - #                       - #          67                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:5:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 23 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:5:                        - - CCATTGCTGC CGGCATCGTG GTC           - #                  - #                    23                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:6:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 46 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:6:                        - - CATGGCTCCA ATGACTCAGA CTACTTCTCT TAAGACTTCT TGGGTT   - #                     46                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:7:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 42 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:7:                        - - AACCCAAGAA GTCTTAAGAG AAGTAGTCTG AGTCATTGGA GC    - #                      - #  42                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:8:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 64 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:8:                        - - AATTCCGTCG TAAACTGACC TTCTATCTGA AAACCTTGGA GAACGCGCAG GC -             #TCAACAGT     60                                                                 - - AATA                 - #                  - #                  - #                 64                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:9:                                     - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 64 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:9:                        - - AGCTTATTAC TGTTGAGCCT GCGCGTTCTC CAAGGTTTTC AGATAGAAGG TC -             #AGTTTACG     60                                                                 - - ACGG                 - #                  - #                  - #                 64                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:10:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 126 amino - #acids                                                (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:10:                       - -      Met Ala Pro Met Thr Gln Thr Thr - # Ser Leu Lys Thr Ser Trp        Val Asn                                                                              1             - #  5                - #   10               - #         15                                                                               - -      Cys Ser Asn Met Ile Asp Glu Ile - # Ile Thr His Leu Lys Gln       Pro Pro                                                                                          20 - #                 25 - #                 30             - -      Leu Pro Leu Leu Asp Phe Asn Asn - # Leu Asn Gly Glu Asp Gln        Asp Ile                                                                                      35     - #             40     - #             45                  - -      Leu Met Glu Asn Asn Leu Arg Arg - # Pro Asn Leu Glu Ala Phe       Asn Arg                                                                                  50         - #         55         - #         60                      - -      Ala Val Lys Ser Leu Gln Asn Ala - # Ser Ala Ile Glu Ser Ile       Leu Lys                                                                              65             - #     70             - #     75             - #         80                                                                            - -      Asn Leu Leu Pro Cys Leu Pro Leu - # Ala Thr Ala Ala Pro Thr        Arg His                                                                                           - #   85               - #   90               - #         95                                                                               - -      Pro Ile His Ile Lys Asp Gly Asp - # Trp Asn Glu Phe Arg Arg       Lys Leu                                                                                          100 - #                105 - #                110            - -      Thr Phe Tyr Leu Lys Thr Leu Glu - # Asn Ala Gln Ala Gln Gln                      115     - #            120     - #            125                 - -  - - (2) INFORMATION FOR SEQ ID NO:11:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:11:                       - - CATGGCTAAC TGCTCTAACA TGAT          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:12:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 22 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:12:                       - - CGATCATGTT AGAGCAGTTA GC           - #                  - #                     22                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:13:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 113 amino - #acids                                                (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:13:                       - -      Met Ala Asn Cys Ser Asn Met Ile - # Asp Glu Ile Ile Thr His        Leu Lys                                                                              1             - #  5                - #   10               - #         15                                                                               - -      Gln Pro Pro Leu Pro Leu Leu Asp - # Phe Asn Asn Leu Asn Gly       Glu Asp                                                                                          20 - #                 25 - #                 30             - -      Gln Asp Ile Leu Met Glu Asn Asn - # Leu Arg Arg Pro Asn Leu        Glu Ala                                                                                      35     - #             40     - #             45                  - -      Phe Asn Arg Ala Val Lys Ser Leu - # Gln Asn Ala Ser Ala Ile       Glu Ser                                                                                  50         - #         55         - #         60                      - -      Ile Leu Lys Asn Leu Leu Pro Cys - # Leu Pro Leu Ala Thr Ala       Ala Pro                                                                              65             - #     70             - #     75             - #         80                                                                            - -      Thr Arg His Pro Ile His Ile Lys - # Asp Gly Asp Trp Asn Glu        Phe Arg                                                                                           - #   85               - #   90               - #         95                                                                               - -      Arg Lys Leu Thr Phe Tyr Leu Lys - # Thr Leu Glu Asn Ala Gln       Ala Gln                                                                                          100 - #                105 - #                110            - -      Gln                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:14:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 amino - #acids                                                 (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:14:                       - -      Met Met Ile Thr Leu Arg Lys Leu - # Pro Leu Ala Val Ala Val        Ala Ala                                                                              1             - #  5                - #   10               - #         15                                                                               - -      Gly Val Met Ser Ala Gln Ala Met - # Ala Asn Cys                                      20 - #                 25                                     - -  - - (2) INFORMATION FOR SEQ ID NO:15:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 133 amino - #acids                                                (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 1                                                               (D) OTHER INFORMATION: - #/note= "Met- may or may not precede     the                                                                                           amino aci - #d in position 1"                                   - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 17                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 17 is Ser,                       Lys, Gly, - # Asp, Met, Gln, or Arg"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 18                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 18 is Asn,                       His, Leu, - # Ile, Phe, Arg, or Gln"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 19                                                              (D) OTHER INFORMATION: - #/note= "Xaa at positiion 19 is Met,                      Phe, Ile, - # Arg, Gly, Ala, or Cys"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 20                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 20 is Ile,                       Cys, Gln, - # Glu, Arg, Pro, or Ala"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 21                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 21 is Asp,                       Phe, Lys, - # Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser,                         or Val"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 22                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 22 is Glu,                       Trp, Pro, - # Ser, Ala, His, Asp, Asn, Gln, Leu, Val,                         or Gly"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 23                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 23 is Ile,                       Val, Ala, - # Leu, Gly, Trp, Lys, Phe, Leu, Ser, or                           Arg"                                                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 24                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 24 is Ile,                       Gly, Val, - # Arg, Ser, Phe, or Leu"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 25                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 25 is Thr,                       His, Gly, - # Gln, Arg, Pro, or Ala"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 26                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 26 is His,                       Thr, Phe, - # Gly, Arg, Ala, or Trp"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 27                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 27 is Leu,                       Gly, Arg, - # Thr, Ser, or Ala"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 28                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 28 is Lys,                       Arg, Leu, - # Gln, Gly, Pro, Val, or Trp"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 29                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 29 is Gln,                       Asn, Leu, - # Pro, Arg, or Val"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 30                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 30 is Pro,                       His, Thr, - # Gly, Asp, Gln, Ser, Leu, or Lys"                  - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 31                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 31 is Pro,                       Asp, Gly, - # Ala, Arg, Leu, or Gln"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 32                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 32 is Leu,                       Val, Arg, - # Gln, Asn, Gly, Ala, or Glu"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 33                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 33 is Pro,                       Leu, Gln, - # Ala, Thr, or Glu"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 34                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 34 is Leu,                       Val, Gly, - # Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe,                         Ile, or - #Met"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 35                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 35 is Leu,                       Ala, Gly, - # Asn, Pro, Gln, or Val"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 36                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 36 is Asp,                       Leu, or - #Val"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 37                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 37 is Phe,                       Ser, Pro, - # Trp, or Ile"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 38                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 38 is Asn,                       or Ala"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 40                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 40 is Leu,                       Trp, or - #Arg"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 41                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 41 is Asn,                       Cys, Arg, - # Leu, His, Met, or Pro"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 42                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 42 is Gly,                       Asp, Ser, - # Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr     - #,                                                                                          Ile, Met, - # or Ala"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 43                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 43 is Glu,                       Asn, Tyr, - # Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly     - #,                                                                                          or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 44                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 44 is Asp,                       Ser, Leu, - # Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala     - #,                                                                                          or Pro"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 45                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 45 is Gln,                       Pro, Phe, - # Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg     - #,                                                                                          Ser, Ala, - # Ile, Glu, or His"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 46                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 46 is Asp,                       Phe, Ser, - # Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr     - #,                                                                                          Ile, Val, - # or Gly"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 47                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 47 is Ile,                       Gly, Val, - # Ser, Arg, Pro, or His"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 48                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 48 is Leu,                       Ser, Cys, - # Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met     - #,                                                                                          Val, or - #Asn"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 49                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 49 is Met,                       Arg, Ala, - # Gly, Pro, Asn, His, or Asp"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 50                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 50 is Glu,                       Leu, Thr, - # Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His     - #,                                                                                          Phe, Met, - # or Gln"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 51                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 51 is Asn,                       Arg, Met, - # Pro, Ser, Thr, or His"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 52                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 52 is Asn,                       His, Arg, - # Leu, Gly, Ser, or Thr"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 53                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 53 is                            Leu, Thr, - # Ala, Gly, Glu, Pro, Lys, Ser, or Met"             - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 54                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 54 is Arg,                       Asp, Ile, - # Ser, Val, Thr, Gln, Asn, Lys, His, Ala,                         or Leu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 55                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 55 is Arg,                       Thr, Val, - # Ser, Leu, or Gly"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 56                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 56 is Pro,                       Gly, Cys, - # Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr,                         Phe, Leu, - # Val, or Lys"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 57                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 57 is Asn                        or Gly"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 58                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 58 is Leu,                       Ser, Asp, - # Arg, Gln, Val, or Cys"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 59                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 59 is Glu,                       Tyr, His, - # Leu, Pro, or Arg"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 60                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 60 is Ala,                       Ser, Pro, - # Tyr, Asn, or Thr"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 61                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 61 is Phe,                       Asn, Glu, - # Pro, Lys, Arg, or Ser"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 62                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 62 is Asn,                       His, Val, - # Arg, Pro, Thr, Asp, or Ile"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 63                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 63 is Arg,                       Tyr, Trp, - # Lys, Ser, His, Pro, or Val"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 64                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 64 is Ala,                       Asn, Pro, - # Ser, or Lys"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 65                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 65 is Val,                       Thr, Pro, - # His, Leu, Phe, or Ser"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 66                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 66 is Lys,                       Ile, Arg, - # Val, Asn, Glu, or Ser"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 67                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 67 is Ser,                       Ala, Phe, - # Val, Gly, Asn, Ile, Pro, or His"                  - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 68                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 68 is Leu,                       Val, Trp, - # Ser, Ile, Phe, Thr, or His"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 69                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 69 is Gln,                       Ala, Pro, - # Thr, Glu, Arg, Trp, Gly, or Leu"                  - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 70                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 70 is Asn,                       Leu, Val, - # Trp, Pro, or Ala"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 71                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 71 is                            Ala,Met,Leu, - #Pro,Arg,Glu,Thr,Gln,Trp,or Asn"                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 72                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 72 is Ser,                       Glu, Met, - # Ala, His, Asn, Arg, or Asp"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 73                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 73 is Ala,                       Glu, Asp, - # Leu, Ser, Gly, Thr, or Arg"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 74                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 74 is Ile,                       Met, Thr, - # Pro, Arg, Gly, or Ala"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 75                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 75 is                            Glu, Lys, - # Gly, Asp, Pro, Trp, Arg, Ser, Gln,                              or Leu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 76                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 76 is Ser,                       Val, Ala, - # Asn, Trp, Glu, Pro, Gly, or Asp"                  - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 77                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 77 is Ile,                       Ser, Arg, - # Thr, or Leu"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 78                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 78 is Leu,                       Ala, Ser, - # Glu, Phe, Gly, or Arg"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 79                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 79 is Lys,       Thr,                                                                                           Asn, Met, - # Arg, Ile, Gly, or Asp"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 80                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 80 is Asn,                      Trp, Val, - # Gly, Thr, Leu, Glu, or Arg"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 81                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 81 is Leu,                       Gln, Gly, - # Ala, Trp, Arg, Val, or Lys"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 82                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 82 is Leu,                       Gln, Lys, - # Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala     - #,                                                                                          Tyr, Phe, - # Ile, Met, or Val"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 83                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 83 is Pro,                       Ala, Thr, - # Trp, Arg, or Met"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 84                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 84 is Cys,                       Glu, Gly, - # Arg, Met, or Val"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 85                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 85 is Leu,                       Asn, Val, - # or Gln"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 86                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 86 is Pro,                       Cys, Arg, - # Ala, or Lys"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 87                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 87 is Leu,                       Ser, Trp, - # or Gly"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 88                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 88 is Ala,                       Lys, Arg, - # Val, or Trp"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 89                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 89 is Thr,                       Asp, Cys, - # Leu, Val, Glu, His, Asn, or Ser"                  - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 90                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 90 is Ala,                       Pro, Ser, - # Thr, Gly, Asp, Ile, or Met"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 91                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 91 is Ala,                       Pro, Ser, - # Thr, Phe, Leu, Asp, or His"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 92                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 92 is Pro,                       Phe, Arg, - # Ser, Lys, His, Ala, Gly, Ile, or Leu"             - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 93                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 93 is Thr,                       Asp, Ser, - # Asn, Pro, Ala, Leu, or Arg"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 94                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 94 is Arg,                       Ile, Ser, - # Glu, Leu, Val, Gln, Lys, His, Ala, or Pro"        - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 95                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 95 is His,                       Gln, Pro, - # Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala     - #,                                                                                          Trp, Phe, - # Ile, or Tyr"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 96                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 96 is Pro,                       Lys, Tyr, - # Gly, Ile, or Thr"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 97                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 97 is Ile,                       Val, Lys, - # Ala, or Asn"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 98                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 98 is His,                       Ile, Asn, - # Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met     - #,                                                                                          Val, Lys, - # Arg, Tyr, or Pro"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 99                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 99 is Ile,                       Leu, Arg, - # Asp, Val, Pro, Gln, Gly, Ser, Phe,                              or His"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 100                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 100 is                           Lys, Tyr, - # Leu, His, Arg, Ile, Ser, Gln, or Pro"             - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 101                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 101 is                           Asp, Pro, - # Met, Lys, His, Thr, Val, Tyr, Glu, Asn, Ser     - #,                                                                                          Ala, Gly, - # Ile, Leu, or Gln"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 102                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 102 is Gly,                      Leu, Glu, - # Lys, Ser, Tyr, or Pro"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 103                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 103 is Asp,                      or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 104                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 104 is                           Trp, Val, - # Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys, Ala     - #,                                                                                          Phe, or - #Gly"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 105                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 105 is                           Asn, Pro, - # Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile     - #,                                                                                          Asp, or - #His"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 106                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 106 is Glu,                      Ser, Ala, - # Lys, Thr, Ile, Gly, or Pro"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 108                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 108 is Arg,                      Lys, Asp, - # Leu, Thr, Ile, Gln, His, Ser, Ala, or Pro"        - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 109                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 109 is Arg,                      Thr, Pro, - # Glu, Tyr, Leu, Ser, or Gly"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 110                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 110 is Lys,                      Ala, Asn, - # Thr, Leu, Arg, Gln, His, Glu, Ser, Ala,                         or Trp"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 111                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 111 is Leu,                      Ile, Arg, - # Asp, or Met"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 112                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 112 is Thr,                      Val, Gln, - # Tyr, Glu, His, Ser, or Phe"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 113                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 113 is Phe,                      Ser, Cys, - # His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val     - #,                                                                                          or Asn"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 114                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 114 is Tyr,                      Cys, His, - # Ser, Trp, Arg, or Leu"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 115                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 115 is                           Leu, Asn, - # Val, Pro, Arg, Ala, His, Thr, Trp, or                           Met"                                                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 116                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 116 is Lys,                      Leu, Pro, - # Thr, Met, Asp, Val, Glu, Arg, Trp, Ser,                         Asn, His, - # Ala, Tyr, Phe, Gln, or Ile"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 117                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 117 is Thr,                      Ser, Asn, - # Ile, Trp, Lys, or Pro"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 118                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 118 is Leu,                      Ser, Pro, - # Ala, Glu, Cys, Asp, or Tyr"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 119                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 119 is Glu,                      Ser, Lys, - # Pro, Leu, Thr, Tyr, or Arg"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 120                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 120 is Asn,                      Ala, Pro, - # Leu, His, Val, or Gln"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 121                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 121 is Ala,                      Ser, Ile, - # Asn, Pro, Lys, Asp, or Gly"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 122                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 122 is                           Gln, Ser, - # Met, Trp, Arg, Phe, Pro, His, Ile, Tyr,                         or  Cy - #s"                                                    - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 123                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 123 is Ala,                      Met, Glu, - # His, Ser, Pro, Tyr, or Leu"                       - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:15:                       - -      Ala Pro Met Thr Gln Thr Thr Ser - # Leu Lys Thr Ser Trp Val        Asn Cys                                                                              1             - #  5                - #   10               - #         15                                                                               - -      Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa - # Xaa Xaa Xaa Xaa Xaa Xaa       Xaa Xaa                                                                                          20 - #                 25 - #                 30             - -      Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa - # Xaa Xaa Xaa Xaa Xaa Xaa        Xaa Xaa                                                                                      35     - #             40     - #             45                  - -      Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa - # Xaa Xaa Xaa Xaa Xaa Xaa       Xaa Xaa                                                                                  50         - #         55         - #         60                      - -      Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa - # Xaa Xaa Xaa Xaa Xaa Xaa       Xaa Xaa                                                                              65             - #     70             - #     75             - #         80                                                                            - -      Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa - # Xaa Xaa Xaa Xaa Xaa Xaa        Xaa Xaa                                                                                           - #   85               - #   90               - #         95                                                                               - -      Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa - # Xaa Xaa Phe Xaa Xaa Xaa       Xaa Xaa                                                                                          100 - #                105 - #                110            - -      Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa - # Xaa Xaa Xaa Gln Gln Thr        Thr Leu                                                                                      115     - #            120     - #            125                 - -      Ser Leu Ala Ile Phe                                                          130                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:16:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 133 amino - #acids                                                (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 1                                                               (D) OTHER INFORMATION: - #/note= "Met- may or may not precede                     the amino - # acid in position 1"                               - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 17                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 17 is Ser,                       Gly, Asp, - # Met, or Gln"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 18                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 18 is Asn,                       His, Leu, - # Ile, Phe, Arg, or Gln"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 19                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 19 is Met,                       Phe, Ile, - # Arg, or Ala"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 20                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 20 is Ile                        or Pro"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 21                                                              (D) OTHER INFORMATION: - #/note; "Xaa at position 21 is Asp                        or Glu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 23                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 23 is Ile,                       Val, Ala, - # Leu, or Gly"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 24                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 24 is Ile,                       Val, Phe, - # or Leu"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 25                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 25 is Thr,                       His, Gly, - # Gln, Arg, Pro, or Ala"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 26                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 26 is His,                       Phe, Gly, - # Arg, or Ala"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 28                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 28 is Lys,                       Leu, Gln, - # Gly, Pro, or Val"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 29                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 29 is Gln,                       Asn, Leu, - # Arg, or Val"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 30                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 30 is Pro,                       His, Thr, - # Gly, or Gln"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 31                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 31 is Pro,                       Asp, Gly, - # Ala, Arg, Leu, or Gln"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 32                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 32 Leu,                          Arg, Gln, - # Asn, Gly, Ala, or Glu"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 33                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 33 is Pro,                       Leu, Gln, - # Ala, or Glu"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 34                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 34 is Leu,                       Val, Gly, - # Ser, Lys, Ala, Arg, Gln, Glu, Ile, Phe,                         Thr, or - #Met"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 35                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 35 is Leu,                       Ala, Asn, - # Pro, Gln, or Val"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 36                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 36 is Asp                        or Leu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 37                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 37 is Phe,                       Ser, Pro, - # Trp, or Ile"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 38                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 38 is Asn                        or Ala"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 41                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 41 is Asn,                       Cys, Arg, - # His, Met, or Pro"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 42                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 42 is Gly,                       Asp, Ser, - # Cys, Ala, Asn, Ile, Leu, Met, Tyr, Val,                         or Arg"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  Modified - #-site                                              (B) LOCATION:  44                                                             (D) OTHER INFORMATION: - # /note="Xaa at position 44 is Asp or     Glu"                                                                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 45                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 45 is Gln,                       Val, Met, - # Leu, Thr, Lys, Ala, Asn, Glu, Ser, or Trp"        - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 46                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 46 is Asp,                       Phe, Ser, - # Thr, Cys, Ala, Asn, Gln, Glu, His, Ile, Lys     - #,                                                                                          Tyr, Val, - # or Gly"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 47                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 47 is Ile,       Val,                                                                                           or His"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 49                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 49 is Met,                      Asn, or - #Asp"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 50                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 50 is Glu,                       Thr, Ala, - # Asn, Ser, or Asp"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 51                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 51 is Asn,                       Arg, Met, - # Pro, Ser, Thr, or His"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 52                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 52 is Asn                        or Gly"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 53                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 53 is Leu,                       Met, or - #Phe"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 54                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 54 is Arg                        Ala, or - #Ser"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 55                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 55 is Arg,                       Thr, Val, - # Leu, or Gly"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 56                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 56 is Pro,                       Gly, Cys, - # Ser, Gln, Ala, Arg, Asn, Glu, His, Leu, Thr     - #,                                                                                          Val, or - #Lys"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 59                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 59 is Glu,                       Tyr, His, - # Leu, or Arg"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 60                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 60 is Ala,                       Ser, Asn, - # or Thr"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 61                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 61 is Phe                        or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 62                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 62 is Asn,                       Val, Pro, - # Thr, or Ile"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 63                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 63 is Arg,                       Tyr, Lys, - # Ser, His, or Val"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 64                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 64 is Ala                        or Asn"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 65                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 65 is Val,                       Thr, Leu, - # or Ser"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 66                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 66 is Lys,                       Ile, Arg, - # Val, Asn, Glu, or Ser"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 67                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 67 is Ser,                       Phe, Val, - # Gly, Asn, Ile, or His"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 68                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 68 is Leu,                       Val, Ile, - # Phe, or His"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 69                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 69 is Gln,                       Ala, Pro, - # Thr, Glu, Arg, or Gly"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 70                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 70 is Asn                        or Pro"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 71                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 71 is Ala,                       Met, Pro, - # Arg, Glu, Thr, or Gln"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 72                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 72 is Ser,                       Glu, Met, - # Ala, His, Asn, Arg, or Asp"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 73                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 73 is Ala,                       Glu, Asp, - # Leu, Ser, Gly, Thr, Arg, or Pro"                  - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 74                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 74 is Ile                        or Met"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 75                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 75 is Glu,                       Gly, Asp, - # Ser, or Gln"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 76                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 76 is Ser,                       Val, Ala, - # Asn, Glu, Pro, Gly, or Asp"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 77                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 77 is Ile,                       Ser, or - #Leu"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 79                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 79 is Lys,                       Thr, Gly, - # Asn, Met, Arg, Ile, Gly, or Asp"                  - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 80                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 80 is Asn,                       Val, Gly, - # Thr, Leu, Glu, or Arg"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 81                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 81 is Leu                        or Val"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 82                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 82 is Leu,                       Gln, Trp, - # Arg, Asp, Ala, Asn, Glu, His, Met, Phe,                         Ser, Thr, - # Tyr, or Val"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 83                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 83 is Pro,                       Ala, Thr, - # Trp, or Met"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 85                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 85 is Leu                        or Val"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 87                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 87 is Leu                        or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 88                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 88 is Ala,                       Arg, or - #Trp"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 89                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 89 is Thr,                       Asp, Glu, - # His, Asn, or Ser"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 90                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 90 is Ala,                       Asp, or - #Met"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 91                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 91 is Ala,                       Pro, Ser, - # Thr, Phe, Leu, or Asp"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 92                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 92 is Pro                        or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 93                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 93 is Thr,                       Asp, Ser, - # Pro, Ala, Leu, or Arg"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 95                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 95 is His,                       Pro, Arg, - # Val, Leu, Gly, Asn, Ile, Phe, Ser,                              or Thr"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 96                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 96 is Pro                        or Tyr"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 97                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 97 is Ile,                       Val, or - #Ala"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 98                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 98 is His,                       Ile, Asn, - # Leu, Asp, Ala, Thr, Leu, Arg, Gln, Glu,                         Lys, Met, - # Ser, Tyr, Val, or Pro"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 99                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 99 is Ile,                       Leu, Val, - # or Phe"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 100                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 100 is Lys,                      Leu, His, - # Arg, Ile, Gln, Pro, or Ser"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 101                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 101 is Asp,                      Pro, Met, - # Lys, His, Thr, Val, Asn, Ile, Leu, or Tyr"        - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 102                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 102 is Gly,                      Glu, Lys, - # or Ser"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 104                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 104 is Trp,                      Val, Tyr, - # Met, or Leu"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 105                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 105 is                           Asn, Pro, - # Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys,                         Ile, Asp - #or His"                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 106                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 106 is Glu,                      Ser, Ala, - # or Gly"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 108                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 108 is Arg,                      Ala, Gln, - # Ser, or Lys"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 109                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 109 is Arg,                      Thr, Glu, - # Leu, Ser, or Gly"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 112                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 112 is Thr,                      Val, Gln, - # Glu, His, or Ser"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 114                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 114 is Tyr                       or Trp"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 115                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 115 is Leu                       or Ala"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 116                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 116 is Lys,                      Thr, Met, - # Val, Trp, Ser, Leu, Ala, Asn, Gln, His, Met     - #,                                                                                          Phe, Tyr, - # or Ile"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 117                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 117 is Thr,                      Ser, or - #Asn"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 119                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 119 is                           Glu, Ser, - # Pro, Leu, Thr, or Tyr"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 120                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 120 is Asn,                      Pro, Leu, - # His, Val, or Gln"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 121                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 121 is Ala,                      Ser, Ile, - # Asn, Pro, Lys, Asp, or Gly"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 122                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 122 is                           Gln, Ser, - # Met, Trp, Arg, Phe, Pro, His, Ile, Tyr,                         or Cys"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 123                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 123 is Ala,                      Met, Glu, - # His, Ser, Pro, Tyr, or Leu"                       - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:16:                       - -      Ala Pro Met Thr Gln Thr Thr Ser - # Leu Lys Thr Ser Trp Val        Asn Cys                                                                              1             - #  5                - #   10               - #         15                                                                               - -      Xaa Xaa Xaa Xaa Xaa Glu Xaa Xaa - # Xaa Xaa Leu Xaa Xaa Xaa       Xaa Xaa                                                                                          20 - #                 25 - #                 30             - -      Xaa Xaa Xaa Xaa Xaa Xaa Asn Leu - # Xaa Xaa Glu Xaa Xaa Xaa        Xaa Leu                                                                                      35     - #             40     - #             45                  - -      Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa - # Asn Leu Xaa Xaa Xaa Xaa       Xaa Xaa                                                                                  50         - #         55         - #         60                      - -      Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa - # Xaa Xaa Xaa Xaa Xaa Leu       Xaa Xaa                                                                              65             - #     70             - #     75             - #         80                                                                            - -      Xaa Xaa Xaa Cys Xaa Pro Xaa Xaa - # Xaa Xaa Xaa Xaa Xaa Arg        Xaa Xaa                                                                                           - #   85               - #   90               - #         95                                                                               - -      Xaa Xaa Xaa Xaa Xaa Xaa Asp Xaa - # Xaa Xaa Phe Xaa Xaa Lys       Leu Xaa                                                                                          100 - #                105 - #                110            - -      Phe Xaa Xaa Xaa Xaa Leu Xaa Xaa - # Xaa Xaa Xaa Gln Gln Thr        Thr Leu                                                                                      115     - #            120     - #            125                 - -      Ser Leu Ala Ile Phe                                                          130                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:17:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 133 amino - #acids                                                (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 1                                                               (D) OTHER INFORMATION: - #/note= "Met- may or may not precede                     the amino - # acid in position 1"                               - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 17                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 17 is Ser,                       Gly, Asp, - # Met, or Gln"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 18                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 18 is Asn,                       His, or - #Ile"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 19                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 19 is Met                        or Ile"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 21                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 21 is Asp                        or Glu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 23                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 23 is Ile,                       Ala, Leu, - # or Gly"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 24                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 24 is Ile,                       Val, or - #Leu"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 25                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 25 is Thr,                       His, Gln, - # or Ala"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 26                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 26 is His                        or Ala"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 29                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 29 is Gln,                       Asn, or - #Val"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 30                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 30 is Pro,                       Gly, or - #Gln"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 31                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 31 is Pro,                       Asp, Gly, - # or Gln"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 32                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 32 is Leu,                       Arg, Gln, - # Asn, Gly, Ala, or Glu"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 33                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 33 is Pro                        or Glu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 34                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 34 is Leu,                       Val, Gly, - # Ser, Lys, Ala, Arg, Gln, Glu, Ile, Phe                          Thr, or - #Met"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 35                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 35 is Leu,                       Ala, Asn, - # Pro, Gln, or Val"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 37                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 37 is Phe,                       Ser, Pro, - # or Trp"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 38                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 38 is Asn                        or Ala"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 42                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 42 is Gly,                       Asp, Ser, - # Cys, Ala, Asn, Ile, Leu, Met, Tyr, or Arg"        - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 45                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 45 is Gln,                       Val, Met, - # Leu, Thr, Ala, Asn, Glu, Ser, or Lys"             - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 46                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 46 is Asp,                       Phe, Ser, - # Thr, Ala, Asn, Gln, Glu, His, Ile, Lys,                         Tyr, Val, - # or Cys"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 50                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 50 is Glu,                       Ala, Asn, - # Ser, or Asp"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 51                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 51 is Asn,                       Arg, Met, - # Pro, Ser, Thr, or His"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 54                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 54 is Arg                        or Ala"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 55                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 55 is Arg,                       Thr, Val, - # Leu, or Gly"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 56                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 56 is Pro,                       Gly, Ser, - # Gln, Ala, Arg, Asn, Glu, Leu, Thr, Val,                         or Lys"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 60                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 60 is Ala                        or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 62                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 62 is Asn,                       Pro, Thr, - # or Ile"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 63                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 63 is Arg                        or Lys"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 64                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 64 is Ala                        or Asn"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 65                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 65 is Val                        or Thr"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 66                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 66 is Lys                        or Arg"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 67                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 67 is Ser                        Phe or - #His"                                                  - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 68                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 68 is Leu,                       Ile, Phe, - # or His"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 69                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 69 is Gln,                       Ala, Pro, - # Thr, Glu, Arg, or Gly"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 71                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 71 is Ala,                       Pro, or - #Arg"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 72                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 72 is Ser,                       Glu, Arg, - # or Asp"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 73                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 73 is Ala                        or Leu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 76                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 76 is Ser,                       Val, Ala, - # Asn, Glu, Pro, or Gly"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 77                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 77 is Ile                        or Leu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 79                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 79 is                            Lys, Thr, - # Gly, Asn, Met, Arg, Ile, Gly, or Asp"             - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 80                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 80 is Asn,                       Gly, Glu, - # or Arg"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 82                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 82 is Leu,                       Gln, Trp, - # Arg, Asp, Ala, Asn, Glu, His, Ile, Met,                         Phe, Ser, - # Thr, Tyr, or Val"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 83                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 83 is Pro                        or Thr"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 85                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 85 is Leu                        or Val"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 87                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 87 is Leu                        or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 88                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 88 is Ala                        or Trp"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 91                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 91 is Ala                        or Pro"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 93                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 93 is Thr,                       Asp, Ser, - # Pro, Ala, Leu, or Arg"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 95                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 95 is His,                       Pro, Arg, - # Val, Leu, Gly, Asn, Phe, Ser, or Thr"             - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 96                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 96 is Pro                        or Tyr"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 97                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 97 is Ile                        or Val"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 98                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 98 is His,                       Ile, Asn, - # Leu, Ala, Thr, Leu, Arg, Gln, Leu, Lys,                         Met, Ser, - # Tyr, Val, or Pro"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 99                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 99 is Ile,                       Leu, or - #Val"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 100                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 100 is Lys,                      Arg, Ile, - # Gln, Pro, or Ser"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 101                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 101 is Asp,                      Pro, Met, - # Lys, His, Thr, Pro, Asn, Ile, Leu, or Tyr"        - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 104                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 104 is Trp                       or Leu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 105                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 105 is                           Asn, Pro, - # Ala, Ser, Trp, Gln, Tyr, Leu, Lys, Ile,                         Asp, or - #His"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 106                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 106 is Glu                       or Gly"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 109                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 109 is Arg,                      Thr, Glu, - # Leu, or Ser"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 112                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 112 is Thr,                      Val, or - #Gln"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 114                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 114 is Tyr                       or Trp"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 115                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 115 is Leu                       or Ala"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 116                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 116 is Lys,                      Thr, Val, - # Trp, Ser, Ala, His, Met, Phe, Tyr, or Ile"        - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 117                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 117 is Thr                       or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 120                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 120 is Asn,                      Pro, Leu, - # His, Val, or Gln"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 121                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 121 is Ala,                      Ser, Ile, - # Asn, Pro, Asp, or Gly"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 122                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 122 is                           Gln, Ser, - # Met, Trp, Arg, Phe, Pro, His, Ile, Tyr,                         or Cys"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 123                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 123 is Ala,                      Met, Glu, - # His, Ser, Pro, Tyr, or Leu"                       - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:17:                       - -      Ala Pro Met Thr Gln Thr Thr Ser - # Leu Lys Thr Ser Trp Val        Asn Cys                                                                              1             - #  5                - #   10               - #         15                                                                               - -      Xaa Xaa Xaa Ile Xaa Glu Xaa Xaa - # Xaa Xaa Leu Lys Xaa Xaa       Xaa Xaa                                                                                          20 - #                 25 - #                 30             - -      Xaa Xaa Xaa Asp Xaa Xaa Asn Leu - # Asn Xaa Glu Xaa Xaa Xaa        Ile Leu                                                                                      35     - #             40     - #             45                  - -      Met Xaa Xaa Asn Leu Xaa Xaa Xaa - # Asn Leu Glu Xaa Phe Xaa       Xaa Xaa                                                                                  50         - #         55         - #         60                      - -      Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa - # Xaa Ile Glu Xaa Xaa Leu       Xaa Xaa                                                                              65             - #     70             - #     75             - #         80                                                                            - -      Leu Xaa Xaa Cys Xaa Pro Xaa Xaa - # Thr Ala Xaa Pro Xaa Arg        Xaa Xaa                                                                                           - #   85               - #   90               - #         95                                                                               - -      Xaa Xaa Xaa Xaa Xaa Gly Asp Xaa - # Xaa Xaa Phe Xaa Xaa Lys       Leu Xaa                                                                                          100 - #                105 - #                110            - -      Phe Xaa Xaa Xaa Xaa Leu Glu Xaa - # Xaa Xaa Xaa Gln Gln Thr        Thr Leu                                                                                      115     - #            120     - #            125                 - -      Ser Leu Ala Ile Phe                                                          130                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:18:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 133 amino - #acids                                                (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 1                                                               (D) OTHER INFORMATION: - #/note= "Met- may or may not precede                     the amino - # acid in position 1"                               - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 17                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 17 is Ser,                       Gly, Asp, - # or Gln"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 18                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 18 is Asn,                       His, or - #Ile"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 23                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 23 is Ile,                       Ala, Leu, - # or Gly"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 25                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 25 is Thr,                       His, or - #Gln"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 26                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 26 is His                        or Ala"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 29                                                              (D) OTHER INFORMATION: - #/note="Xaa at position 29 is Gln                         or Asn"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 30                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 30 is Pro                        or Gly"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 32                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 32 is Leu,                       Arg, Asn, - # or Ala"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 34                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 34 is Leu,                       Val, Ser, - # Ala, Arg, Gln, Glu, Ile, Phe, Thr, or Met"        - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 35                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 35 is Leu,                       Ala, Asn, - # or Pro"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 38                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 38 is Asn                        or Ala"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 42                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 42 is Gly,                       Asp, Ser, - # Ala, Asn, Ile, Leu, Met, Tyr, or Arg"             - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 45                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 45 is Gln,                       Val, Met, - # Leu, Ala, Asn, Glu, or Lys"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 46                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 46 is Asp,                       Phe, Ser, - # Ala, Gln, Glu, His, Val, or Thr"                  - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 50                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 50 is Glu,                       Asn, Ser, - # or Asp"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 51                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 51 is Asn,                       Arg, Pro, - # Thr, or His"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 55                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 55 is Arg,                       Leu, or - #Gly"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 56                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 56 is Pro,                       Gly, Ser, - # Ala, Asn, Val, Leu, or Gln"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 62                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 62 is Asn,                       Pro, or - #Thr"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 64                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 64 is Ala                        or Asn"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 65                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 65 is Val                        or Thr"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 67                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 67 is Ser                        or Phe"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 68                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 68 is Leu                        or Phe"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 69                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 69 is Gln,                       Ala, Glu, - # or Arg"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 76                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 76 is Ser,                       Val, Asn, - # Pro, or Gly"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 77                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 77 is Ile                        or Leu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 79                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 79 is Lys,                       Gly, Asn, - # Met, Arg, Ile, or Gly"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 80                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 80 is Asn,                       Gly, Glu, - # or Arg"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 82                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 82 is Leu,                       Gln, Trp, - # Arg, Asp, Asn, Glu, His, Met, Phe, Ser,                         Thr, Tyr, - # or Val"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 87                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 87 is Leu                        or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 88                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 88 is Ala                        or Trp"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 91                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 91 is Ala                        or Pro"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 93                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 93 is Thr,                       Asp, or - #Ala"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 95                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 95 is His,                       Pro, Arg, - # Val, Gly, Asn, Ser, or Thr"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 98                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 98 is His,                       Ile, Asn, - # Ala, Thr, Arg, Gln, Glu, Lys, Met, Ser,                         Tyr, Val, - # or Leu"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 99                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 99 is Ile                        or Leu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 100                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 100 is Lys                       or Arg"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION:  101                                                            (D) OTHER INFORMATION: - #/note= "Xaa at position 101 is Asp,                      Pro, Met, - # Lys, Thr, His, Pro, Asn, Ile, Leu, or Tyr"        - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 105                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 105 is Asn,                      Pro, Ser, - # Ile, or Asp"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  Modified - #-site                                              (B) LOCATION:  108                                                            (D) OTHER INFORMATION: - # /note= "Xaa at position 108 is Arg,     Ala,                                                                                          or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 109                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 109 is Arg,                      Thr, Glu, - # Leu, or Ser"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 112                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 112 is Thr                       or Gln"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 116                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 116 is Lys,                      Val, Trp, - # Ala, His, Phe, Tyr, or Ile"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 117                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 117 is Thr                       or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 120                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 120 is Asn,                      Pro, Leu, - # His, Val, or Gln"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 121                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 121 is Ala,                      Ser, Ile, - # Pro, or Asp"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 122                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 122 is Gln,                      Met, Trp, - # Phe, Pro, His, Ile, or Tyr"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 123                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 123 is Ala,                      Met, Glu, - # Ser, or Leu"                                      - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:18:                       - -      Ala Pro Met Thr Gln Thr Thr Ser - # Leu Lys Thr Ser Trp Val        Asn Cys                                                                              1             - #  5                - #   10               - #         15                                                                               - -      Xaa Xaa Met Ile Asp Glu Xaa Ile - # Xaa Xaa Leu Lys Xaa Xaa       Pro Xaa                                                                                          20 - #                 25 - #                 30             - -      Pro Xaa Xaa Asp Phe Xaa Asn Leu - # Asn Xaa Glu Asp Xaa Xaa        Ile Leu                                                                                      35     - #             40     - #             45                  - -      Met Xaa Xaa Asn Leu Arg Xaa Xaa - # Asn Leu Glu Ala Phe Xaa       Arg Xaa                                                                                  50         - #         55         - #         60                      - -      Xaa Lys Xaa Xaa Xaa Asn Ala Ser - # Ala Ile Glu Xaa Xaa Leu       Xaa Xaa                                                                              65             - #     70             - #     75             - #         80                                                                            - -      Leu Xaa Pro Cys Leu Pro Xaa Xaa - # Thr Ala Xaa Pro Xaa Arg        Xaa Pro                                                                                           - #   85               - #   90               - #         95                                                                               - -      Ile Xaa Xaa Xaa Xaa Gly Asp Trp - # Xaa Glu Phe Xaa Xaa Lys       Leu Xaa                                                                                          100 - #                105 - #                110            - -      Phe Tyr Leu Xaa Xaa Leu Glu Xaa - # Xaa Xaa Xaa Gln Gln Thr        Thr Leu                                                                                      115     - #            120     - #            125                 - -      Ser Leu Ala Ile Phe                                                          130                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:19:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 111 amino - #acids                                                (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 1                                                               (D) OTHER INFORMATION: - #/note= "Met- or Met-Ala- may or may                     not prece - #de the amino acid in position 1"                   - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 3                                                               (D) OTHER INFORMATION: - #/note= "Xaa at position 3 is Ser,                        Lys, Gly, - # Asp, Met, Gln, or Arg"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 4                                                               (D) OTHER INFORMATION: - #/note= "Xaa at position 4 is Asn,                        His, Leu, - # Ile, Phe, Arg, or Gln"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 5                                                               (D) OTHER INFORMATION: - #/note= "Xaa at position 5 is Met,                        Phe, Ile, - # Arg, Gly, Ala, or Cys"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 6                                                               (D) OTHER INFORMATION: - #/note= "Xaa at position 6 is Ile,                        Cys, Gln, - # Glu, Arg, Pro, or Ala"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 7                                                               (D) OTHER INFORMATION: - #/note= "Xaa at position 7 is Asp,                        Phe, Lys, - # Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser,                         or Val"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 8                                                               (D) OTHER INFORMATION: - #/note= "Xaa at position 8 is Glu,                        Trp, Pro, - # Ser, Ala, His, Asp, Asn, Gln, Leu, Val,                         or Gly"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 9                                                               (D) OTHER INFORMATION: - #/note= "Xaa at position 9 is                             Ile, Val, - # Ala, Leu, Gly, Trp, Lys, Phe, Leu, Ser                          or Arg"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 10                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 10 is Ile,                       Gly, Val, - # Arg, Ser, Phe, or Leu"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 11                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 11 is Thr,                       His, Gly, - # Gln, Arg, Pro, or Ala"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 12                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 12 is His,                       Thr, Phe, - # Gly, Arg, Ala, or Trp"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 13                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 13 is Leu,                       Gly, Arg, - # Thr, Ser, or Ala"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 14                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 14 is Lys,                       Arg, Leu, - # Gln, Gly, Pro, Val, or Trp"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 15                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 15 is Gln,                       Asn, Leu, - # Pro, Arg, or Val"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 16                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 16 is Pro,                       His, Thr, - # Gly, Asp, Gln, Ser, Leu, or Lys"                  - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 17                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 17 is Pro,                       Asp, Gly, - # Ala, Arg, Leu, or Gln"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 18                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 18 is Leu,                       Val, Arg, - # Gln, Asn, Gly, Ala, or Glu"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 19                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 19 is Pro,                       Leu, Gln, - # Ala, Thr, or Glu"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 20                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 20 is Leu,                       Val, Gly, - # Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe,                         Ile, or - #Met"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 21                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 21 is Leu,                       Ala, Gly, - # Asn, Pro, Gln, or Val"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 22                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 22 is Asp,                       Leu, or - #Val"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 23                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 23 is Phe,                       Ser, Pro, - # Trp, or Ile"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 24                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 24 is Asn                        or Ala"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 26                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 26 is Leu,                       Trp, or - #Arg"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 27                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 27 is Asn,                       Cys, Arg, - # Leu, His, Met, or Pro"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 28                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 28 is Gly,                       Asp, Ser, - # Cys, Ala, Lys, Asn, Thr, Leu, Val, Glu,                         Phe, Tyr, - # Ile, or Met"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 29                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 29 is Glu,                       Asn, Tyr, - # Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr,                         Gly, or - #Ser"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 30                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 30 is Asp,                       Ser, Leu, - # Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln,                         Ala, or - #Pro"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 31                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 31 is Gln,                       Pro, Phe, - # Val, Met, Leu, Thr, Lys, Asp, Asn, Arg,                         Ser, Ala, - # Ile, Glu, His, or Trp"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 32                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 32 is Asp,                       Phe, Ser, - # Thr, Cys, Glu, Asn, Gln, Lys, His, Ala,                         Tyr, Ile, - # Val, or Gly"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 33                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 33 is Ile,                       Gly, Val, - # Ser, Arg, Pro, or His"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 34                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 34 is Leu,                       Ser, Cys, - # Arg, Ile, His, Phe, Glu, Lys, Thr, Ala,                         Met, Val, - # or Asn"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 35                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 35 is Met,                       Arg, Ala, - # Gly, Pro, Asn, His, or Asp"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 36                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 36 is Glu,                       Leu, Thr, - # Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val,                         His, Phe, - # Met, or Gln"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 37                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 37 is Asn,                       Arg, Met, - # Pro, Ser, Thr, or His"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 38                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 38 is Asn,                       His, Arg, - # Leu, Gly, Ser, or Thr"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 39                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 39 is                            Leu, Thr, - # Ala, Gly, Glu, Pro, Lys, Ser, or Met"             - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 40                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 40 is Arg,                       Asp, Ile, - # Ser, Val, Thr, Gln, Asn, Lys, His,                              Ala, or - #Leu"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 41                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 41 is Arg,                       Thr, Val, - # Ser, Leu, or Gly"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 42                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 42 is Pro,                       Gly, Cys, - # Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr,                         Phe, Leu, - # Val, or Lys"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 43                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 43 is Asn                        or Gly"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 44                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 44 is Leu,                       Ser, Asp, - # Arg, Gln, Val, or Cys"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 45                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 45 is Glu,                       Tyr, His, - # Leu, Pro, or Arg"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 46                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 46 is Ala,                       Ser, Pro, - # Tyr, Asn, or Thr"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 47                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 47 is Phe,                       Asn, Glu, - # Pro, Lys, Arg, or Ser"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 48                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 48 is Asn,                       His, Val, - # Arg, Pro, Thr, Asp, or Ile"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 49                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 49 is Arg,                       Tyr, Trp, - # Lys, Ser, His, Pro, or Val"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 50                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 50 is Ala,                       Asn, Pro, - # Ser, or Lys"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 51                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 51 is Val,                       Thr, Pro, - # His, Leu, Phe, or Ser"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 52                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 52 is Lys,                       Ile, Arg, - # Val, Asn, Glu, or Ser"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 53                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 53 is Ser,                       Ala, Phe, - # Val, Gly, Asn, Ile, Pro, or His"                  - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 54                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 54 is Leu,                       Val, Trp, - # Ser, Ile, Phe, Thr, or His"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 55                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 55 is Gln,                       Ala, Pro, - # Thr, Glu, Arg, Trp, Gly, or Leu"                  - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 56                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 56 is Asn,                       Leu, Val, - # Trp, Pro, or Ala"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 57                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 57 is Ala,                       Met, Leu, - # Pro, Arg, Glu, Thr, Gln, Trp, or Asn"             - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 58                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 58 is Ser,                       Glu, Met, - # Ala, His, Asn, Arg, or Asp"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 59                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 59 is Ala,                       Glu, Asp, - # Leu, Ser, Gly, Thr, or Arg"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 60                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 60 is Ile,                       Met, Thr, - # Pro, Arg, Gly, Ala"                               - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 61                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 61 is                            Glu, Lys, - # Gly, Asp, Pro, Trp, Arg, Ser, Gln,                              or Leu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 62                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 62 is Ser,                       Val, Ala, - # Asn, Trp, Glu, Pro, Gly, or Asp"                  - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 63                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 63 is Ile,                       Ser, Arg, - # Thr, or Leu"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 64                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 64 is Leu,                       Ala, Ser, - # Glu, Phe, Gly, or Arg"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 65                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 65 is Lys,                       Thr, Gly, - # Asn, Met, Arg, Ile, or Asp"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 66                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 66 is Asn,                       Trp, Val, - # Gly, Thr, Leu, Glu, or Arg"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 67                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 67 is Leu,                       Gln, Gly, - # Ala, Trp, Arg, Val, or Lys"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 68                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 68 is Leu,                       Gln, Lys, - # Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala     - #,                                                                                          Tyr, Phe, - # Ile, Met, or Val"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 69                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 69 is Pro,                       Ala, Thr, - # Trp, Arg, or Met"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 70                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 70 is Cys,                       Glu, Gly, - # Arg, Met, or Val"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 71                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 71 is Leu,                       Asn, Val, - # or Gln"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 72                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 72 is Pro,                       Cys, Arg, - # Ala, or Lys"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 73                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 73 is Leu,                       Ser, Trp, - # or Gly"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 74                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 74 is Ala,                       Lys, Arg, - # Val, or Trp"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 75                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 75 is Thr,                       Asp, Cys, - # Leu, Val, Glu, His, Asn, or Ser"                  - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 76                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 76 is Ala,                       Pro, Ser, - # Thr, Gly, Asp, Ile, or Met"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 77                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 77 is Ala,                       Pro, Ser, - # Thr, Phe, Leu, Asp, or His"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 78                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 78 is Pro,                       Phe, Arg, - # Ser, Lys, His, Ala, Gly, Ile, or Leu"             - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 79                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 79 is Thr,                       Asp, Ser, - # Asn, Pro, Ala, Leu, or Arg"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 80                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 80 is Arg,                       Ile, Ser, - # Glu, Leu, Val, Gln, Lys, His, Ala, or Pro"        - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 81                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 81 is His,                       Gln, Pro, - # Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser,                         Ala, Trp, - # Phe, Ile, or Tyr"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 82                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 82 is Pro,                       Lys, Tyr, - # Gly, Ile, or Thr"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 83                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 83 is Ile,                       Val, Lys, - # Ala, or Asn"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 84                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 84 is His,                       Ile, Asn, - # Leu, Asp, Ala, Thr, Glu, Gln, Ser,                              Phe, Met, - # Val, Lys, Arg, Tyr, or Pro"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 85                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 85 is                            Ile, Leu, - # Arg, Asp, Val, Pro, Gln, Gly, Ser,                              Phe, or - #His"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 86                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 86 is                            Lys, Tyr, - # Leu, His, Arg, Ile, Ser, Gln, or Pro"             - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 87                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 87 is                            Asp, Pro, - # Met, Lys, His, Thr, Val, Tyr, Glu, Asn,                         Ser, Ala, - # Gly, Ile, Leu, or Gln"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 88                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 88 Gly,                          Leu, Glu, - # Lys, Ser, Tyr, or Pro"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 89                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 89 is Asp                        or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 90                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 90 is                            Trp, Val, - # Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys,                         Ala, Phe, - # or Gly"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 91                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 91 is                            Asn, Pro, - # Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys,                         Ile, Asp, - # or His"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 92                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 92 is Glu,                       Ser, Ala, - # Lys, Thr, Ile, Gly, or Pro"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 94                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 94 is Arg,                       Lys, Asp, - # Leu, Thr, Ile, Gln, His, Ser, Ala, or Pro"        - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 95                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 95 is Arg,                       Thr, Pro, - # Glu, Tyr, Leu, Ser, or Gly"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 96                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 96 is Lys,                       Asn, Thr, - # Leu, Gln, Arg, His, Glu, Ser, Ala,                              or Trp"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 97                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 97 is Leu,                       Ile, Arg, - # Asp, or Met"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 98                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 98 is Thr,                       Val, Gln, - # Tyr, Glu, His, Ser, or Phe"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 99                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 99 is Phe,                       Ser, Cys, - # His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile,                         Val, or - #Asn"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 100                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 100 is Tyr,                      Cys, His, - # Ser, Trp, Arg, or Leu"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 101                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 101 is Leu,                      Asn, Val, - # Pro, Arg, Ala, His, Thr, Trp, or Met"             - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 102                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 102 is                           Lys, Leu, - # Pro, Thr, Met, Asp, Val, Glu, Arg, Trp,                         Ser, Asn, - # His, Ala, Tyr, Phe, Gln, or Ile"                  - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 103                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 103 is Thr,                      Ser, Asn, - # Ile, Trp, Lys, or Pro"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 104                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 104 is Leu,                      Ser, Pro, - # Ala, Glu, Cys, Asp, or Tyr"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 105                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 105 is Glu,                      Ser, Lys, - # Pro, Leu, Thr, Tyr, or Arg"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 106                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 106 is Asn,                      Ala, Pro, - # Leu, His, Val or Gln"                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 107                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 107 is Ala,                      Ser, Ile, - # Asn, Pro, Lys, Asp, or Gly"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 108                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 108 is                           Gln, Ser, - # Met, Trp, Arg, Phe, Pro, His, Ile, Tyr,                         or Cys"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 109                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 109 is Ala,                      Met, Glu, - # His, Ser, Pro, Tyr, or Leu"                       - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:19:                       - -      Asn Cys Xaa Xaa Xaa Xaa Xaa Xaa - # Xaa Xaa Xaa Xaa Xaa Xaa        Xaa Xaa                                                                              1             - #  5                - #   10               - #         15                                                                               - -      Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa - # Asn Xaa Xaa Xaa Xaa Xaa       Xaa Xaa                                                                                          20 - #                 25 - #                 30             - -      Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa - # Xaa Xaa Xaa Xaa Xaa Xaa        Xaa Xaa                                                                                      35     - #             40     - #             45                  - -      Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa - # Xaa Xaa Xaa Xaa Xaa Xaa       Xaa Xaa                                                                                  50         - #         55         - #         60                      - -      Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa - # Xaa Xaa Xaa Xaa Xaa Xaa       Xaa Xaa                                                                              65             - #     70             - #     75             - #         80                                                                            - -      Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa - # Xaa Xaa Xaa Xaa Phe Xaa        Xaa Xaa                                                                                           - #   85               - #   90               - #         95                                                                               - -      Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa - # Xaa Xaa Xaa Xaa Xaa Gln       Gln                                                                                              100 - #                105 - #                110            - -  - - (2) INFORMATION FOR SEQ ID NO:20:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 111 amino - #acids                                                (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 1                                                               (D) OTHER INFORMATION: - #/note= "Met- or Met-Ala- may or may                      not prece - #de the amino acid in position 1"                   - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 3                                                               (D) OTHER INFORMATION: - #/note= "Xaa at position 3 is Ser,                        Gly, Asp, - # Met, or Gln"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 4                                                               (D) OTHER INFORMATION: - #/note= "Xaa at position 4 is Asn,                        His, Leu, - # Ile, Phe, Arg, or Gln"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 5                                                               (D) OTHER INFORMATION: - #/note= "Xaa at position 5 is Met,                        Phe, Ile, - # Arg, or Ala"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 6                                                               (D) OTHER INFORMATION: - #/note= "Xaa at position 6 is Ile or                      Pro"                                                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 7                                                               (D) OTHER INFORMATION: - #/note= "Xaa at position 7 is Asp or                      Glu"                                                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 9                                                               (D) OTHER INFORMATION: - #/note= "Xaa at position 9 is Ile,                        Val, Ala, - # Leu, or Gly"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 10                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 10 is Ile,                       Val, Phe, - # or Leu"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 11                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 11 is Thr,                       His, Gly, - # Gln, Arg, Pro, or Ala"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 12                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 12 is His,                       Phe, Gly, - # Arg, or Ala"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 14                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 14 is Lys,                       Leu, Gln, - # Gly, Pro, or Val"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 15                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 15 is Gln,                       Asn, Leu, - # Arg, or Val"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 16                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 16 is Pro,                       His, Thr, - # Gly, or Gln"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 17                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 17 is Pro,                       Asp, Gly, - # Ala, Arg, Leu, or Gln"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 18                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 18 is Leu,                       Arg, Gln, - # Asn, Gly, Ala or Glu"                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 19                                                              (D) OTHER INFORMATION: - #/note= "Xaa at poisiton 19 is Pro,                       Leu, Gln, - # Ala, or Glu"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 20                                                              (D) OTHER INFORMATION: - #/note= "Xaa at positon 20 is Leu,                        Val, Gly, - # Ser, Lys, Ala, Arg, Gln, Glu, Ile, Phe,                         Thr, or - #Met"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 21                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 21 is Leu,                       Ala, Asn, - # Pro, Gln, or Val"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 22                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 22 is Asp                        or Leu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 23                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 23 is Phe,                       Ser, Pro, - # Trp, or Ile"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 24                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 24 is Asn                        or Ala"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 27                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 27 is Asn,                       Cys, Arg, - # His, Met, or Pro"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 28                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 28 is Gly,                       Asp, Ser, - # Cys, Ala, Asn, Ile, Leu, Met, Tyr, or Arg"        - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 30                                                              (C) OTHER INFORMATION: - # /note= "Xaa at position 30 is Asp                       or Glu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 31                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 31 is Gln,                       Val, Met, - # Leu, Thr, Lys, Ala, Asn, Glu, Ser, or Trp"        - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 32                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 32 is Asp,                       Phe, Ser, - # Thr, Cys, Ala, Asn, Gln, Glu, His, Ile,                         Lys, Tyr, - # Val, or Gly"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 33                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 33 is Ile,                       Val, or - #His"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 35                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 35 is Met,                       Asn, or - #Asp"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 36                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 36 is Glu,                       Thr, Ala, - # Asn, Ser, or Asp"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 37                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 37 is Asn,                       Arg, Met, - # Pro, Ser, Thr, or His"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 38                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 38 is Asn                        or Gly"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 39                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 39 is Leu,                       Met, or - #Phe"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 40                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 40 is Arg,                       Ala, or - #Ser"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 41                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 41 is Arg,                       Thr, Val, - # Leu, or Gly"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 42                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 42 is Pro,                       Gly, Cys, - # Ser, Gln, Ala, Arg, Asn, Glu, His, Leu,                         Thr, Val, - # or Lys"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 45                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 45 is Glu,                       Tyr, His, - # Leu, or Arg"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 46                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 46 is Ala,                       Ser, Asn, - # or Thr"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 47                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 47 is Phe                        or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 48                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 48 is Asn,                       Val, Pro, - # Thr, or Ile"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 49                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 49 is Arg,                       Tyr, Lys, - # Ser, His, or Val"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 50                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 50 is Ala                        or Asn"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 51                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 51 is Val,                       Thr, Leu, - # or Ser"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 52                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 52 is Lys,                       Ile, Arg, - # Val, Asn, Glu, or Ser"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 53                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 53 is Ser,                       Phe, Val, - # Gly, Asn, Ile, or His"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 54                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 54 is Leu,                       Val, Ile, - # Phe, or His"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 55                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 55 is Gln,                       Ala, Pro, - # Thr, Glu, Arg, or Gly"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 56                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 56 is Asn                        or Pro"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 57                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 57 is Ala,                       Met, Pro, - # Arg, Glu, Thr, or Gln"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 58                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 58 is Ser,                       Glu, Met, - # Ala, His, Asn, Arg, or Asp"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 59                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 59 is Ala,                       Glu, Asp, - # Leu, Ser, Gly, Thr, Arg, or Pro"                  - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 60                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 60 is Ile                        or Met"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 61                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 61 is Glu,                       Gly, Asp, - # Ser, or Gln"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 62                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 62 is Ser,                       Val, Ala, - # Asn, Glu, Pro, Gly, or Asp"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 63                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 63 is Ile,                       Ser, or - #Leu"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 65                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 65 is Lys,                       Thr, Gly, - # Asn, Met, Arg, Ile, or Asp"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 66                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 66 is Asn,                       Val, Gly, - # Thr, Leu, Glu, or Arg"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 67                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 67 is Leu                        or Val"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 68                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 68 is Leu,                       Gln, Trp, - # Arg, Asp, Ala, Asn, Glu, His, Met, Phe,                         Ser, Thr, - # Tyr, or Val"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 69                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 69 is Pro,                       Ala, Thr, - # Trp, or Met"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 71                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 71 is Leu                        or Val"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 73                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 73 is Leu                        or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 74                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 74 is Ala,                       Arg, or - #Trp"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 75                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 75 is Thr,                       Asp, Glu, - # His, Asn, or Ser"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 76                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 76 is Ala,                       Asp, or - #Met"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 77                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 77 is Ala,                       Pro, Ser, - # Thr, Phe, Leu, or Asp"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 78                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 78 is Pro                        or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 79                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 79 is Thr,                       Asp, Ser, - # Pro, Ala, Leu, or Arg"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 81                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 81 is His,                       Pro, Arg, - # Val, Leu, Gly, Asn, Ile, Phe, Ser, or Thr"        - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 82                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 82 is Pro                        or Tyr"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 83                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 83 is Ile,                       Val, or - #Ala"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 84                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 84 is His,                       Ile, Asn, - # Leu, Asp, Ala, Thr, Arg, Gln, Glu, Lys,                         Met, Ser, - # Tyr, Val, or Pro"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 85                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 85 is Ile,                       Leu, Val, - # or Phe"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 86                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 86 is Lys,                       Leu, His, - # Arg, Ile, Gln, Pro, or Ser"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 87                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 87 is Asp,                       Pro, Met, - # Lys, His, Thr, Val, Asn, Ile, Leu, or Tyr"        - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 88                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 88 is Gly,                       Glu, Lys, - # or Ser"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 90                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 90 is Trp,                       Val, Tyr, - # Met, or Leu"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 91                                                              (D) OTHER INFORMATION: - #/note=                                                   "Xaa a - #t position 91 is Asn, Pro, Ala, Phe, Ser,                           Trp, Gln, - # Tyr, Leu, Lys, Ile, Asp, or His"                  - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 92                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 92 is Glu,                       Ser, Ala, - # or Gly"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 94                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 94 is Arg,                       Ala, Gln, - # Ser, or Lys"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 95                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 95 Arg,                          Thr, Glu, - # Leu, Ser, or Gly"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 98                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 98 is Thr,                       Val, Gln, - # Glu, His, or Ser"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 100                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 100 is Tyr                       or Trp"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 101                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 101 is Leu                       or Ala"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 102                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 102 is Lys,                      Thr, Met, - # Val, Trp, Ser, Leu, Ala, Asn, Gln, His,                         Met, Phe, - # Tyr, or Ile"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 103                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 103 is Thr,                      Ser, or - #Asn"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 105                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 105 is Glu,                      Ser, Pro, - # Leu, Thr, or Tyr"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 106                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 106 is Asn,                      Pro, Leu, - # His, Val, or Gln"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 107                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 107 is Ala,                      Ser, Ile, - # Asn, Pro, Lys, Asp, or Gly"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 108                                                             (D) OTHER INFORMATION: - #/note=                                                   "Xaa a - #t position 108 is Gln, Ser, Met, Trp, Arg, P -      #he,                                                                                           Pro, His, - # Ile, Tyr, or Cys"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 109                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 109 is Ala,                     Met, Glu, - # His, Ser, Pro, Tyr, or Leu"                       - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:20:                       - -      Asn Cys Xaa Xaa Xaa Xaa Xaa Glu - # Xaa Xaa Xaa Xaa Leu Xaa        Xaa Xaa                                                                              1             - #  5                - #   10               - #         15                                                                               - -      Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa - # Asn Leu Xaa Xaa Glu Xaa       Xaa Xaa                                                                                          20 - #                 25 - #                 30             - -      Xaa Leu Xaa Xaa Xaa Xaa Xaa Xaa - # Xaa Xaa Asn Leu Xaa Xaa        Xaa Xaa                                                                                      35     - #             40     - #             45                  - -      Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa - # Xaa Xaa Xaa Xaa Xaa Xaa       Xaa Leu                                                                                  50         - #         55         - #         60                      - -      Xaa Xaa Xaa Xaa Xaa Cys Xaa Pro - # Xaa Xaa Xaa Xaa Xaa Xaa       Xaa Arg                                                                              65             - #     70             - #     75             - #         80                                                                            - -      Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa - # Asp Xaa Xaa Xaa Phe Xaa        Xaa Lys                                                                                           - #   85               - #   90               - #         95                                                                               - -      Leu Xaa Phe Xaa Xaa Xaa Xaa Leu - # Xaa Xaa Xaa Xaa Xaa Gln       Gln                                                                                              100 - #                105 - #                110            - -  - - (2) INFORMATION FOR SEQ ID NO:21:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 111 amino - #acids                                                (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 1                                                               (D) OTHER INFORMATION: - #/note= "Met- or Met-Ala- may or may                      not prece - #de the amino acid in position 1"                   - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 3                                                               (D) OTHER INFORMATION: - #/note= "Xaa at position 3 is Ser,                        Gly, Asp, - # Met, or Gln"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 4                                                               (D) OTHER INFORMATION: - #/note= "Xaa at position 4 is Asn,                        His, or - #Ile"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 5                                                               (D) OTHER INFORMATION: - #/note= "Xaa at position 5 is Met                         or Ile"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 7                                                               (C) OTHER INFORMATION: - #/note= "Xaa at position 7 is Asp or      Glu"                                                                             - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 9                                                               (D) OTHER INFORMATION: - #/note= "Xaa at position 9 is Ile,                       Ala, Leu, - # or Gly"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 10                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 10 is Ile,                       Val, or - #Leu"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 11                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 11 is Thr,                       His, Gln, - # or Ala"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 12                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 12 is His                        or Ala"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 15                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 15 is Gln,                       Asn, or - #Val"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 16                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 16 is Pro,                       Gly, or - #Gln"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 17                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 17 is Pro,                       Asp, Gly, - # or Gln"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 18                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 18 is Leu,                       Arg, Gln, - # Asn, Gly, Ala, or Glu"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 19                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 19 is Pro                        or Glu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 20                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 20 is Leu,                       Val, Gly, - # Ser, Lys, Ala, Arg, Gln, Glu, Ile, Phe,                         Thr, or - #Met"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 21                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 21 is Leu,                       Ala, Asn, - # Pro, Gln, or Val"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 23                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 23 is Phe,                       Ser, Pro, - # or Trp"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 24                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 24 is Asn                        or Ala"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 28                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 28 is Gly,                       Asp, Ser, - # Cys, Ala, Asn, Ile, Leu, Met, Tyr, or Arg"        - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 30                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 30 is Asp                        or Glu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 31                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 31 is Gln,                       Val, Met, - # Leu, Thr, Ala, Asn, Glu, Ser, or Lys"             - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 32                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 32 is Asp,                       Phe, Ser, - # Thr, Ala, Asn, Gln, Glu, His, Ile, Lys,                         Tyr, Val, - # or Cys"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 36                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 36 is Glu,                       Ala, Asn, - # Ser, or Asp"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 37                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 37 is Asn,                       Arg, Met, - # Pro, Ser, Thr, or His"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 40                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 40 is Arg                        or Ala"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 41                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 41 is Arg,                       Thr, Val, - # Leu, or Gly"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 42                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 42 is Pro,                       Gly, Ser, - # Gln, Ala, Arg, Asn, Glu, Leu, Thr, Val,                         or Lys"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 46                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 46 is Ala                        or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 48                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 48 is Asn,                       Pro,  - #Thr, or Ile"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 49                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 49 is Arg                        or Lys"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 50                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 50 is Ala                        or Asn"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 51                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 51 is Val                        or Thr"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 52                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 52 is Lys                        or Arg"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 53                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 53 is Ser,                       Phe, or - #His"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 54                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 54 is Leu,                       Ile, Phe, - # or His"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 55                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 55 is Gln,                       Ala, Pro, - # Thr, Glu, Arg, or Gly"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 57                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 57 is Ala,                       Pro, or - #Arg"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 58                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 58 is Ser,                       Glu, Arg, - # or Asp"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 59                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 59 is Ala                        or Leu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 62                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 62 is Ser,                       Val, Ala, - # Asn, Glu, Pro, or Gly"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 63                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 63 is Ile                        or Leu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 65                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 65 is Lys,                       Thr, Gly, - # Asn, Met, Arg, Ile, Gly, or Asp"                  - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 66                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 66 is Asn,                       Gly, Glu, - # or Arg"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 68                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 68 is Leu,                       Gln, Trp, - # Arg, Asp, Ala, Asn, Glu, His, Ile, Met,                         Phe, Ser, - # Thr, Tyr, or Val"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 69                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 69 is Pro                        or Thr"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 71                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 71 is Leu                        or Val"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 73                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 73 is Leu                        or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 74                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 74 is Ala                        or Trp"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 77                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 77 is Ala                        or Pro"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 79                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 79 is Thr,                       Asp, Ser, - # Pro, Ala, Leu, or Arg"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 81                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 81 is His,                       Pro, Arg, - # Val, Leu, Gly, Asn, Phe, Ser, or Thr"             - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 82                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 82 is Pro                        or Tyr"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 83                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 83 is Ile                        or Val"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 84                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 84 is His,                       Ile, Asn, - # Leu, Ala, Thr, Leu, Arg, Gln, Leu, Lys,                         Met, Ser, - # Tyr, Val, or Pro"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 85                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 85 is Ile,                       Leu, or - #Val"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 86                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 86 is Lys,                       Arg, Ile, - # Gln, Pro, or Ser"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 87                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 87 is Asp,                       Pro, Met, - # Lys, His, Thr, Asn, Ile, Leu, or Tyr"             - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 90                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 90 is Trp                        or Leu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 91                                                              (D) OTHER INFORMATION: - #/note="Xaa at position 91 is Asn,                        Pro, Ala, - # Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp,                         or His"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 92                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 92 is Glu                        or Gly"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 94                                                              (C) OTHER INFORMATION: - #/note= "Xaa at position 94 is Arg,                       Ala, or - #Ser"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 95                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 95 is Arg,                       Thr, Glu, - # Leu, or Ser"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 98                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 98 is Thr,                       Val, or - #Gln"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 100                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 100 is Tyr                       or Trp"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 101                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 101 is Leu                       or Ala"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 102                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 102 is Lys,                      Thr, Val, - # Trp, Ser, Ala, His, Met, Phe, Tyr, or Ile"        - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 103                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 103 is Thr                       or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 106                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 106 is Asn,                      Pro, Leu, - # His, Val, or Gln"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 107                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 107 is Ala,                      Ser, Ile, - # Asn, Pro, Asp, or Gly"                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 108                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 108 is Gln,                      Ser, Met, - # Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys"        - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 109                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 109 is Ala,                      Met, Glu, - # His, Ser, Pro, Tyr, or Leu"                       - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:21:                       - -      Asn Cys Xaa Xaa Xaa Ile Xaa Glu - # Xaa Xaa Xaa Xaa Leu Lys        Xaa Xaa                                                                              1             - #  5                - #   10               - #         15                                                                               - -      Xaa Xaa Xaa Xaa Xaa Asp Xaa Xaa - # Asn Leu Asn Xaa Glu Xaa       Xaa Xaa                                                                                          20 - #                 25 - #                 30             - -      Ile Leu Met Xaa Xaa Asn Leu Xaa - # Xaa Xaa Asn Leu Glu Xaa        Phe Xaa                                                                                      35     - #             40     - #             45                  - -      Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn - # Xaa Xaa Xaa Ile Glu Xaa       Xaa Leu                                                                                  50         - #         55         - #         60                      - -      Xaa Xaa Leu Xaa Xaa Cys Xaa Pro - # Xaa Xaa Thr Ala Xaa Pro       Xaa Arg                                                                              65             - #     70             - #     75             - #         80                                                                            - -      Xaa Xaa Xaa Xaa Xaa Xaa Xaa Gly - # Asp Xaa Xaa Xaa Phe Xaa        Xaa Lys                                                                                           - #   85               - #   90               - #         95                                                                               - -      Leu Xaa Phe Xaa Xaa Xaa Xaa Leu - # Glu Xaa Xaa Xaa Xaa Gln       Gln                                                                                              100 - #                105 - #                110            - -  - - (2) INFORMATION FOR SEQ ID NO:22:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 111 amino - #acids                                                (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 1                                                               (D) OTHER INFORMATION: - #/note= "Met- or Met-Ala- may or may                      not prece - #de the amino acid in position 1"                   - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 3                                                               (D) OTHER INFORMATION: - #/note= "Xaa at position 3 is Ser,                        Gly, Asp, - # or Gln"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 4                                                               (D) OTHER INFORMATION: - #/note= "Xaa at position 4 is Asn,                        His, or - #Ile"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 9                                                               (D) OTHER INFORMATION: - #/note= "Xaa at position 9 is Ile,                        Ala, Leu, - # or Gly"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 11                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 11 is Thr,                       His, or - #Gln"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 12                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 12 is His                        or Ala"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 15                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 15 is Gln                        or Asn"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 16                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 16 is Pro                        or Gly"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 18                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 18 is Leu,                       Arg, Asn, - # or Ala"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 20                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 20 is Leu,                       Val, Ser, - # Ala, Arg, Gln, Glu, Ile, Phe, Thr, or Met"        - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 21                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 21 is Leu,                       Ala, Asn, - # or Pro"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 24                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 24 is Asn                        or Ala"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 28                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 28 is Gly,                       Asp, Ser, - # Ala, Asn, Ile, Leu, Met, Tyr, or Arg"             - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 31                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 31 is Gln,                       Val, Met, - # Leu, Ala, Asn, Glu, or Lys"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 32                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 32 is Asp,                       Phe, Ser, - # Ala, Gln, Glu, His, Val, or Thr"                  - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 36                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 36 is Glu,                       Asn, Ser, - # or Asp"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 37                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 37 is Asn,                       Arg, Pro, - # Thr, or His"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 41                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 41 is Arg,                       Leu, or - #Gly"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 42                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 42 is Pro,                       Gly, Ser, - # Ala, Asn, Val, Leu, or Gln"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 48                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 48 is Asn,                       Pro, or - #Thr"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 50                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 50 is Ala                        or Asn"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 51                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 51 is Val                        or Thr"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 53                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 53 is Ser                        or Phe"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 54                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 54 is Leu                        or Phe"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 55                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 55 is Gln,                       Ala, Glu, - # or Arg"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 62                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 62 is Ser,                       Val, Asn, - # Pro, or Gly"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 63                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 63 is Ile                        or Leu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 65                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 65 is Lys,                       Asn, Met, - # Arg, Ile, or Gly"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 66                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 66 is Asn,                       Gly, Glu, - # or Arg"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 68                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 68 is Leu,                       Gln, Trp, - # Arg, Asp, Asn, Glu, His, Met, Phe, Ser,                         Thr, Tyr, - # or Val"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 73                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 73 is Leu                        or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 74                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 74 is Ala                        or Trp"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 77                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 77 is Ala                        or Pro"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 79                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 79 is Thr,                       Asp, or - #Ala"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 81                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 81 is His,                       Pro, Arg, - # Val, Gly, Asn, Ser, or Thr"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 84                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 84 is His,                       Ile, Asn, - # Ala, Thr, Arg, Gln, Glu, Lys, Met,                              Ser, Tyr, - # Val, or Leu"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 85                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 85 is Ile                        or Leu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 86                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 86 is Lys                        or Arg"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 87                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 87 is Asp,                       Pro, Met, - # Lys, His, Pro, Asn, Ile, Leu, or Tyr"             - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 91                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 91 is Asn,                       Pro, Ser, - # Ile, or Asp"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 94                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 94 is Arg,                       Ala, or - #Ser"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 95                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 95 is Arg,                       Thr, Glu, - # Leu, or Ser"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 98                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 98 is Thr                        or Gln"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 102                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 102 is Lys,                      Val, Trp, - # or Ile"                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 103                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 103 is Thr,                      Ala, His, - # Phe, Tyr, or Ser"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 106                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 106 is Asn,                      Pro, Leu, - # His, Val, or Gln"                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 107                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 107 is Ala,                      Ser, Ile, - # Pro, or Asp"                                      - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 108                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 108 is Gln,                      Met, Trp, - # Phe, Pro, His, Ile, or Tyr"                       - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 109                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 109 is Ala,                      Met, Glu, - # Ser, or Leu"                                      - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:22:                       - -      Asn Cys Xaa Xaa Met Ile Asp Glu - # Xaa Ile Xaa Xaa Leu Lys        Xaa Xaa                                                                              1             - #  5                - #   10               - #         15                                                                               - -      Pro Xaa Pro Xaa Xaa Asp Phe Xaa - # Asn Leu Asn Xaa Glu Asp       Xaa Xaa                                                                                          20 - #                 25 - #                 30             - -      Ile Leu Met Xaa Xaa Asn Leu Arg - # Xaa Xaa Asn Leu Glu Ala        Phe Xaa                                                                                      35     - #             40     - #             45                  - -      Arg Xaa Xaa Lys Xaa Xaa Xaa Asn - # Ala Ser Ala Ile Glu Xaa       Xaa Leu                                                                                  50         - #         55         - #         60                      - -      Xaa Xaa Leu Xaa Pro Cys Leu Pro - # Xaa Xaa Thr Ala Xaa Pro       Xaa Arg                                                                              65             - #     70             - #     75             - #         80                                                                            - -      Xaa Pro Ile Xaa Xaa Xaa Xaa Gly - # Asp Trp Xaa Glu Phe Xaa        Xaa Lys                                                                                           - #   85               - #   90               - #         95                                                                               - -      Leu Xaa Phe Tyr Leu Xaa Xaa Leu - # Glu Xaa Xaa Xaa Xaa Gln       Gln                                                                                              100 - #                105 - #                110            - -  - - (2) INFORMATION FOR SEQ ID NO:23:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 111 amino - #acids                                                (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 1                                                               (D) OTHER INFORMATION: - #/note= "Met- or Met-Ala- may or may                      not prece - #de the amino acid in position 1"                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:23:                       - -      Asn Cys Ser Asn Met Ile Asp Glu - # Ile Ile Thr His Leu Lys        Gln Pro                                                                              1             - #  5                - #   10               - #         15                                                                               - -      Pro Leu Pro Leu Leu Asp Phe Asn - # Asn Leu Asn Gly Glu Asp       Gln Asp                                                                                          20 - #                 25 - #                 30             - -      Ile Leu Met Glu Asn Asn Leu Arg - # Arg Pro Asn Leu Glu Ala        Phe Asn                                                                                      35     - #             40     - #             45                  - -      Arg Ala Val Lys Ser Leu Gln Asn - # Ala Ser Ala Ile Glu Ser       Ile Leu                                                                                  50         - #         55         - #         60                      - -      Lys Asn Leu Leu Pro Cys Leu Pro - # Leu Ala Thr Ala Ala Pro       Thr Arg                                                                              65             - #     70             - #     75             - #         80                                                                            - -      His Pro Ile His Ile Lys Asp Gly - # Asp Trp Asn Glu Phe Arg        Arg Lys                                                                                           - #   85               - #   90               - #         95                                                                               - -      Leu Thr Phe Tyr Leu Lys Thr Leu - # Glu Asn Ala Gln Ala Gln       Gln                                                                                              100 - #                105 - #                110            - -  - - (2) INFORMATION FOR SEQ ID NO:24:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 58 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:24:                       - - CTAGCCACGG CCGCACCCAC GCGACATCCA ATCCATATCA AGGACGGTGA CT - #GGAATG           58                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:25:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 58 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:25:                       - - TTAACATTCC AGTCACCGTC CTTGATATGG ATTGGATGTC GCGTGGGTGC GG - #CCGTGG           58                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:26:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 20 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:26:                       - - TGTCTGCTCA GGCCATGGCT            - #                  - #                      - # 20                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:27:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 67 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:27:                       - - GCGCGAATTC ATTCCAGTCA CCGTCCTTGA TATGGTCGAC TTATTACGTG GG -             #TGCGGCCG     60                                                                 - - TGGCTAG                 - #                  - #                       - #          67                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:28:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 55 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:28:                       - - GCGCGAATTC ATTCCAGTCA CCGTCGACTT ATTAGATTGG ATGTCGCGTG GG - #TGC              55                                                                       - -  - - (2) INFORMATION FOR SEQ ID NO:29:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 16 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:29:                       - - TGAACCATAT GTCAGG             - #                  - #                      - #    16                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:30:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:30:                       - - AATTCCTGAC ATATGGTTCA TGCA          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:31:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 43 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:31:                       - - GCGCGAATTC GTCGACTTAT TAGTCCTTGA TATGGATTGG ATG    - #                      - # 43                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:32:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 67 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:32:                       - - GCGCGAATTC ATTCCAGTCA CCGTCCTTGA TATGGATTGG ATGSNNCGTG GG -             #TGCGGCCG     60                                                                 - - TGGCTAG                 - #                  - #                       - #          67                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:33:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 64 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:33:                       - - GCGCGAATTC ATTCCAGTCA CCGTCCTTGA TATGGATTGG SNNTCGCGTG GG -            #TGCGGCCG     60                                                                 - - TGGC                 - #                  - #                  - #                 64                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:34:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 61 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:34:                       - - GCGCGAATTC ATTCCAGTCA CCGTCCTTGA TATGGATSNN ATGTCGCGTG GG -             #TGCGGCCG     60                                                                 - - T                  - #                  - #                  - #                   61                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:35:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 58 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:35:                       - - GCGCGAATTC ATTCCAGTCA CCGTCCTTGA TATGSNNTGG ATGTCGCGTG GG - #TGCGGC           58                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:36:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:36:                       - - GATATGGATT GGATGTCGCG TGGG          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:37:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 55 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:37:                       - - GCGCGAATTC ATTCCAGTCA CCGTCCTTGA TSNNGATTGG ATGTCGCGTG GG - #TGC              55                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:38:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 52 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:38:                       - - GCGCGAATTC ATTCCAGTCA CCGTCCTTSN NATGGATTGG ATGTCGCGTG GG - #                 52                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:39:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 49 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:39:                       - - GCGCGAATTC ATTCCAGTCA CCGTCSNNGA TATGGATTGG ATGTCGCGT  - #                   49                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:40:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 46 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:40:                       - - GCGCGAATTC ATTCCAGTCA CCSNNCTTGA TATGGATTGG ATGTCG   - #                     46                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:41:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:41:                       - - GTCACCGTCC TTGATATGGA TTGG          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:42:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 43 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:42:                       - - GCGCGAATTC ATTCCAGTCS NNGTCCTTGA TATGGATTGG ATG    - #                      - # 43                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:43:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 40 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:43:                       - - GCGCGAATTC ATTCCASNNA CCGTCCTTGA TATGGATTGG     - #                      - #    40                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:44:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:44:                       - - GCGCGAATTC ATTSNNGTCA CCGTCCTTGA TATGGAT      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:45:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 34 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:45:                       - - GCGCGAATTC SNNCCAGTCA CCGTCCTTGA TATG       - #                  -     #        34                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:46:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 25 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:46:                       - - GAATTCATTC CAGTCACCGT TCCTT          - #                  - #                   25                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:47:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 26 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:47:                       - - CGCGCGGAAT TCATTCCAGT CACCGT          - #                  - #                  26                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:48:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 42 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:48:                       - - CGCGCGCCAT GGCTAACTGC ATTATAACAC ACACTTAAAG CA    - #                      - #  42                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:49:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 58 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:49:                       - - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAACA GCCACCTTTG CC - #TTTGCT           58                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:50:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 76 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:50:                       - - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TATAACACAC TT -             #AAAGCTGG     60                                                                 - - ACTTCAACAA CCTCAA             - #                  - #                      - #    76                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:51:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 50 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:51:                       - - GCGCGCGATA TCTTGGTCTT CTTCACCATT CAGCGGCAGC GGTGGCTGCT  - #                  50                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:52:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 65 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:52:                       - - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT ATTTTCCATC AGGATGAGGT TG -             #TTGAAGTC     60                                                                 - - CAGCA                 - #                  - #                  -      #            65                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:53:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 47 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:53:                       - - GCGCGCCTCG AGGTTTGGAC GACGAAGATC TTGGTCTTCA CCATTGA   - #                    47                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:54:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 68 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:54:                       - - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCACGGTTG AATGCCTCGT TA -             #TTTTCCAT     60                                                                 - - CAGGATAT                - #                  - #                       - #          68                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:55:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 50 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:55:                       - - GCGCGCTGAT GCATTCTGCA GAGACTTGAC GAGGTTTGGA CGACGAAGGT  - #                  50                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:56:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 47 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:56:                       - - GCGCGCCTCG AGGCATTCAA CCGTGCTGCA TCAGCAATTG AGAGCAT   - #                    47                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:57:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 35 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:57:                       - - GCGCGCCTGC AGAATATTCT TAAAAATCTC CTGCC       - #                  -     #       35                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:58:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 53 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:58:                       - - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCCCATGTC TGCCGCTAGC CA - #C                53                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:59:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 71 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:59:                       - - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTCTTA AAAATCTCCT GA -             #CGGCCGCA     60                                                                 - - CCCACGCGAC A               - #                  - #                      - #       71                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:60:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 67 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:60:                       - - CGCGCGGAAT TCATTCCAGT CACCGTCCTT GATATGGATT GGATGTCGCA GG -             #GCAGACAT     60                                                                 - - GGCAGGA                 - #                  - #                       - #          67                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:61:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 78 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:61:                       - - CGCGCGAAGC TTATTACTGT TGAGCCTGCG CGTTCTCCAA GGTTTTCAGA TA -            #GAAGGTAT     60                                                                 - - TCCAGTCACC GTCCTTGA             - #                  - #                      - #  78                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:62:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 60 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:62:                       - - CGCGCGAAGC TTATTACTGT TGAGCCTGCG CGTTCTCCAA CAGTTTACGA CG -             #GAATTCAT     60                                                                 - -  - - (2) INFORMATION FOR SEQ ID NO:63:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 42 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:63:                       - - CGCGCGAAGC TTATTACTGT TGGGTTTTCA GATAGAAGGT CA    - #                      - #  42                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:64:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 58 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:64:                       - - CGCGCGCCAT GGCTAACTGC NNSAACATGA TCGATGAAAT TATAACACAC TT - #AAAGCA           58                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:65:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 111 amino - #acids                                                (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:65:                       - -      Asn Cys Ser Asn Met Ile Asp Glu - # Ile Ile Thr His Leu Lys        Gln Pro                                                                              1             - #  5                - #   10               - #         15                                                                               - -      Pro Leu Pro Leu Leu Asp Phe Asn - # Asn Leu Asn Gly Glu Asp       Gln Asp                                                                                          20 - #                 25 - #                 30             - -      Ile Leu Met Glu Asn Asn Leu Arg - # Arg Pro Asn Leu Glu Ala        Phe Asn                                                                                      35     - #             40     - #             45                  - -      Arg Ala Val Lys Ser Leu Gln Asn - # Ala Ser Ala Ile Glu Ser       Ile Leu                                                                                  50         - #         55         - #         60                      - -      Lys Asn Leu Leu Pro Cys Leu Pro - # Leu Ala Thr Ala Ala Pro       Thr Arg                                                                              65             - #     70             - #     75             - #         80                                                                            - -      His Pro Ile His Ile Lys Asp Gly - # Asp Trp Asn Glu Phe Arg        Arg Lys                                                                                           - #   85               - #   90               - #         95                                                                               - -      Leu Thr Phe Tyr Leu Lys Thr Leu - # Glu Asn Ala Gln Ala Gln       Gln                                                                                              100 - #                105 - #                110            - -  - - (2) INFORMATION FOR SEQ ID NO:66:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 113 amino - #acids                                                (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:66:                       - -      Met Ala Asn Cys Ser Asn Met Ile - # Asp Glu Ile Ile Thr His        Leu Lys                                                                              1             - #  5                - #   10               - #         15                                                                               - -      Gln Pro Pro Leu Pro Leu Leu Asp - # Phe Asn Asn Leu Asn Gly       Glu Asp                                                                                          20 - #                 25 - #                 30             - -      Gln Asp Ile Leu Met Glu Asn Asn - # Leu Arg Arg Pro Asn Leu        Glu Ala                                                                                      35     - #             40     - #             45                  - -      Phe Asn Arg Ala Val Lys Ser Leu - # Gln Asn Ala Ser Ala Ile       Glu Ser                                                                                  50         - #         55         - #         60                      - -      Ile Leu Lys Asn Leu Leu Pro Cys - # Leu Pro Leu Ala Thr Ala       Ala Pro                                                                              65             - #     70             - #     75             - #         80                                                                            - -      Thr Arg His Pro Ile Ile Ile Arg - # Asp Gly Asp Trp Asn Glu        Phe Arg                                                                                           - #   85               - #   90               - #         95                                                                               - -      Arg Lys Leu Thr Phe Tyr Leu Lys - # Thr Leu Glu Asn Ala Gln       Ala Gln                                                                                          100 - #                105 - #                110            - -      Gln                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:67:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 113 amino - #acids                                                (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:67:                       - -      Met Ala Asn Cys Ser Asn Met Ile - # Asp Glu Ile Ile Thr His        Leu Lys                                                                              1             - #  5                - #   10               - #         15                                                                               - -      Gln Pro Pro Leu Pro Leu Leu Asp - # Phe Asn Asn Leu Asn Gly       Glu Asp                                                                                          20 - #                 25 - #                 30             - -      Gln Asp Ile Leu Met Glu Asn Asn - # Leu Arg Arg Pro Asn Leu        Glu Ala                                                                                      35     - #             40     - #             45                  - -      Phe Asn Arg Ala Val Lys Ser Leu - # Gln Asn Ala Ser Ala Ile       Glu Ser                                                                                  50         - #         55         - #         60                      - -      Ile Leu Lys Asn Leu Leu Pro Cys - # Leu Pro Leu Ala Thr Ala       Ala Pro                                                                              65             - #     70             - #     75             - #         80                                                                            - -      Thr Arg Arg Pro Ile Ile Ile Arg - # Asp Gly Asp Trp Asn Glu        Phe Arg                                                                                           - #   85               - #   90               - #         95                                                                               - -      Arg Lys Leu Thr Phe Tyr Leu Lys - # Thr Leu Glu Asn Ala Gln       Ala Gln                                                                                          100 - #                105 - #                110            - -      Gln                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:68:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 339 base - #pairs                                                 (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: double                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (genomic)                                     - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:68:                       - - ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA GC -             #CACCGCTG     60                                                                 - - CCGCTGCTGG ACTTCAACAA CCTCAATGAC GAAGACATGT CTATCCTGAT GG -            #AAAATAAC    120                                                                 - - CTTCGTCGTC CAAACCTCGA GGCATTCAAC CGTGCTGTCA AGTCTCTGCA GA -            #ATGCATCA    180                                                                 - - GCAATTGAGA GCATTCTTAA AAATCTCCTG CCATGTCTGC CCCTGGCCAC GG -            #CCGCACCC    240                                                                 - - ACGCGACATC CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TA -            #AACTGACC    300                                                                 - - TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAG      - #                      - #   339                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:69:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 113 amino - #acids                                                (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:69:                       - -      Met Ala Asn Cys Ser Asn Met Ile - # Asp Glu Ile Ile Thr His        Leu Lys                                                                              1             - #  5                - #   10               - #         15                                                                               - -      Gln Pro Pro Leu Pro Leu Leu Asp - # Phe Asn Asn Leu Asn Asp       Glu Asp                                                                                          20 - #                 25 - #                 30             - -      Met Ser Ile Leu Met Glu Asn Asn - # Leu Arg Arg Pro Asn Leu        Glu Ala                                                                                      35     - #             40     - #             45                  - -      Phe Asn Arg Ala Val Lys Ser Leu - # Gln Asn Ala Ser Ala Ile       Glu Ser                                                                                  50         - #         55         - #         60                      - -      Ile Leu Lys Asn Leu Leu Pro Cys - # Leu Pro Leu Ala Thr Ala       Ala Pro                                                                              65             - #     70             - #     75             - #         80                                                                            - -      Thr Arg His Pro Ile His Ile Lys - # Asp Gly Asp Trp Asn Glu        Phe Arg                                                                                           - #   85               - #   90               - #         95                                                                               - -      Arg Lys Leu Thr Phe Tyr Leu Lys - # Thr Leu Glu Asn Ala Gln       Ala Gln                                                                                          100 - #                105 - #                110            - -      Gln                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:70:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 45 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:70:                       - - CTTTAAGTGT GTTATAATTT CGTTGATCAT GTTAGAGCAG TTAGC   - #                      - #45                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:71:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 40 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:71:                       - - CATGGCTAAC TGCTCTAACA TGATCCAAGA AATTATAACA     - #                      - #    40                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:72:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 45 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:72:                       - - CTTTAAGTGT GTTATAATTT CTTGGATCAT GTTAGAGCAG TTAGC   - #                      - #45                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:73:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 40 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:73:                       - - CATGGCTAAC TGCTCTAACA TGATCGAAGA AATTATAACA     - #                      - #    40                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:74:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 76 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:74:                       - - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TATAACANNS TT -             #AAAGCAGC     60                                                                 - - CACCTTTGCC TTTGCT             - #                  - #                      - #    76                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:75:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 76 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:75:                       - - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TATAACACAC NN -             #SAAGCAGC     60                                                                 - - CACCTTTGCC TTTGCT             - #                  - #                      - #    76                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:76:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 76 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:76:                       - - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TATAACACAC TT -             #ANNSCAGC     60                                                                 - - CACCTTTGCC TTTGCT             - #                  - #                      - #    76                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:77:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 94 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:77:                       - - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TATAACACAC TT -             #AAAGNNSC     60                                                                 - - CACCTTTGCC TTTGCTGGAC TTCAACAACC TCAA       - #                  -     #        94                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:78:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 94 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:78:                       - - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TATAACACAC TT -             #AAAGCAGN     60                                                                 - - NSCCTTTGCC TTTGCTGGAC TTCAACAACC TCAA       - #                  -     #        94                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:79:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 94 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:79:                       - - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TATAACACAC TT -             #AAAGCAGC     60                                                                 - - CANNSTTGCC TTTGCTGGAC TTCAACAACC TCAA       - #                  -     #        94                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:80:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 94 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:80:                       - - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TATAACACAC TT -             #AAAGCAGC     60                                                                 - - CACCTNNSCC TTTGCTGGAC TTCAACAACC TCAA       - #                  -     #        94                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:81:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 94 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:81:                       - - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TATAACACAC TT -             #AAAGCAGC     60                                                                 - - CACCTTTGNN STTGCTGGAC TTCAACAACC TCAA       - #                  -     #        94                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:82:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 94 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:82:                       - - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TATAACACAC TT -             #AAAGCAGC     60                                                                 - - CACCTTTGCC TNNSCTGGAC TTCAACAACC TCAA       - #                  -     #        94                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:83:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 65 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:83:                       - - GCGCGCGATA TCTTGGTCTT CACCATTGAG GTTGTTGAAG TCSNNCAGCG GC -             #AGCGGTGG     60                                                                 - - CTGCT                 - #                  - #                  -      #            65                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:84:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 65 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:84:                       - - GCGCGCGATA TCTTGGTCTT CACCATTGAG GTTGTTGAAS NNCAGCAGCG GC -            #AGCGGTGG     60                                                                 - - CTGCT                 - #                  - #                  -      #            65                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:85:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 65 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:85:                       - - GCGCGCGATA TCTTGGTCTT CACCATTGAG GTTGTTSNNG TCCAGCAGCG GC -            #AGCGGTGG     60                                                                 - - CTGCT                 - #                  - #                  -      #            65                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:86:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 65 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:86:                       - - GCGCGCGATA TCTTGGTCTT CACCATTGAG GTTSNNGAAG TCCAGCAGCG GC -            #AGCGGTGG     60                                                                 - - CTGCT                 - #                  - #                  -      #            65                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:87:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 65 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:87:                       - - GCGCGCGATA TCTTGGTCTT CACCATTGAG SNNGTTGAAG TCCAGCAGCG GC -            #AGCGGTGG     60                                                                 - - CTGCT                 - #                  - #                  -      #            65                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:88:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 65 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:88:                       - - GCGCGCGATA TCTTGGTCTT CACCATTSNN GTTGTTGAAG TCCAGCAGCG GC -            #AGCGGTGG     60                                                                 - - CTGCT                 - #                  - #                  -      #            65                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:89:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 83 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:89:                       - - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT ATTTTCCATC AGGATATCTT GG -            #TCTTCACC     60                                                                 - - SNNGAGGTTG TTGAAGTCCA GCA           - #                  - #                    83                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:90:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 83 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:90:                       - - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT ATTTTCCATC AGGATATCTT GG -             #TCTTCSNN     60                                                                 - - ATTGAGGTTG TTGAAGTCCA GCA           - #                  - #                    83                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:91:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 83 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:91:                       - - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT ATTTTCCATC AGGATATCTT GG -             #TCSNNACC     60                                                                 - - ATTGAGGTTG TTGAAGTCCA GCA           - #                  - #                    83                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:92:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 83 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:92:                       - - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT ATTTTCCATC AGGATATCTT GS -             #NNTTCACC     60                                                                 - - ATTGAGGTTG TTGAAGTCCA GCA           - #                  - #                    83                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:93:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 83 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:93:                       - - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT ATTTTCCATC AGGATATCSN NG -             #TCTTCACC     60                                                                 - - ATTGAGGTTG TTGAAGTCCA GCA           - #                  - #                    83                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:94:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 83 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:94:                       - - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT ATTTTCCATC AGGATSNNTT GG -             #TCTTCACC     60                                                                 - - ATTGAGGTTG TTGAAGTCCA GCA           - #                  - #                    83                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:95:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 65 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:95:                       - - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT ATTTTCCATC AGSNNATCTT GG -             #TCTTCACC     60                                                                 - - ATTGA                 - #                  - #                  -      #            65                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:96:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 65 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:96:                       - - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT ATTTTCCATS NNGATATCTT GG -            #TCTTCACC     60                                                                 - - ATTGA                 - #                  - #                  -      #            65                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:97:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 65 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:97:                       - - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT ATTTTCSNNC AGGATATCTT GG -            #TCTTCACC     60                                                                 - - ATTGA                 - #                  - #                  -      #            65                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:98:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 65 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:98:                       - - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT ATTSNNCATC AGGATATCTT GG -            #TCTTCACC     60                                                                 - - ATTGA                 - #                  - #                  -      #            65                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:99:                                    - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 65 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:99:                       - - GCGCGCCTCG AGGTTTGGAC GACGAAGGTT SNNTTCCATC AGGATATCTT GG -            #TCTTCACC     60                                                                 - - ATTGA                 - #                  - #                  -      #            65                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:100:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 65 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:100:                      - - GCGCGCCTCG AGGTTTGGAC GACGAAGSNN ATTTTCCATC AGGATATCTT GG -            #TCTTCACC     60                                                                 - - ATTGA                 - #                  - #                  -      #            65                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:101:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 86 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:101:                      - - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCACGGTTG AATGCCTCGA GG -            #TTTGGACG     60                                                                 - - ACGSNNGTTA TTTTCCATCA GGATAT          - #                  - #                  86                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:102:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 86 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:102:                      - - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCACGGTTG AATGCCTCGA GG -             #TTTGGACG     60                                                                 - - SNNAAGGTTA TTTTCCATCA GGATAT          - #                  - #                  86                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:103:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 86 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:103:                      - - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCACGGTTG AATGCCTCGA GG -             #TTTGGSNN     60                                                                 - - ACGAAGGTTA TTTTCCATCA GGATAT          - #                  - #                  86                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:104:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 86 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:104:                      - - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCACGGTTG AATGCCTCGA GG -             #TTSNNACG     60                                                                 - - ACGAAGGTTA TTTTCCATCA GGATAT          - #                  - #                  86                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:105:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 86 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:105:                      - - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCACGGTTG AATGCCTCGA GS -             #NNTGGACG     60                                                                 - - ACGAAGGTTA TTTTCCATCA GGATAT          - #                  - #                  86                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:106:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 86 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:106:                      - - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCACGGTTG AATGCCTCSN NG -             #TTTGGACG     60                                                                 - - ACGAAGGTTA TTTTCCATCA GGATAT          - #                  - #                  86                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:107:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 68 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:107:                      - - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCACGGTTG AATGCSNNGA GG -             #TTTGGACG     60                                                                 - - ACGAAGGT                - #                  - #                       - #          68                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:108:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 68 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:108:                      - - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCACGGTTG AASNNCTCGA GG -            #TTTGGACG     60                                                                 - - ACGAAGGT                - #                  - #                       - #          68                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:109:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 68 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:109:                      - - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCACGGTTS NNTGCCTCGA GG -            #TTTGGACG     60                                                                 - - ACGAAGGT                - #                  - #                       - #          68                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:110:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 68 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:110:                      - - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCACGSNNG AATGCCTCGA GG -            #TTTGGACG     60                                                                 - - ACGAAGGT                - #                  - #                       - #          68                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:111:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 68 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:111:                      - - GCGCGCTGAT GCATTCTGCA GAGACTTGAC AGCSNNGTTG AATGCCTCGA GG -            #TTTGGACG     60                                                                 - - ACGAAGGT                - #                  - #                       - #          68                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:112:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 68 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:112:                      - - GCGCGCTGAT GCATTCTGCA GAGACTTGAC SNNACGGTTG AATGCCTCGA GG -            #TTTGGACG     60                                                                 - - ACGAAGGT                - #                  - #                       - #          68                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:113:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 65 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:113:                      - - GCGCGCCTCG AGGCATTCAA CCGTGCTNNS AAGTCTCTGC AGAATGCATC AG -            #CAATTGAG     60                                                                 - - AGCAT                 - #                  - #                  -      #            65                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:114:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 65 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:114:                      - - GCGCGCCTCG AGGCATTCAA CCGTGCTGTC NNSTCTCTGC AGAATGCATC AG -            #CAATTGAG     60                                                                 - - AGCAT                 - #                  - #                  -      #            65                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:115:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 65 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:115:                      - - GCGCGCCTCG AGGCATTCAA CCGTGCTGTC AAGNNSCTGC AGAATGCATC AG -            #CAATTGAG     60                                                                 - - AGCAT                 - #                  - #                  -      #            65                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:116:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 65 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:116:                      - - GCGCGCCTCG AGGCATTCAA CCGTGCTGTC AAGTCTNNSC AGAATGCATC AG -            #CAATTGAG     60                                                                 - - AGCAT                 - #                  - #                  -      #            65                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:117:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 65 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:117:                      - - GCGCGCCTCG AGGCATTCAA CCGTGCTGTC AAGTCTCTGN NSAATGCATC AG -            #CAATTGAG     60                                                                 - - AGCAT                 - #                  - #                  -      #            65                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:118:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 65 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:118:                      - - GCGCGCCTCG AGGCATTCAA CCGTGCTGTC AAGTCTCTGC AGNNSGCATC AG -            #CAATTGAG     60                                                                 - - AGCAT                 - #                  - #                  -      #            65                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:119:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 53 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:119:                      - - GCGCGCCTGC AGAATNNSTC AGCAATTGAG AGCATTCTTA AAAATCTCCT GC - #C                53                                                                       - -  - - (2) INFORMATION FOR SEQ ID NO:120:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 53 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:120:                      - - GCGCGCCTGC AGAATGCANN SGCAATTGAG AGCATTCTTA AAAATCTCCT GC - #C                53                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:121:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 53 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:121:                      - - GCGCGCCTGC AGAATGCATC ANNSATTGAG AGCATTCTTA AAAATCTCCT GC - #C                53                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:122:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 53 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:122:                      - - GCGCGCCTGC AGAATGCATC AGCANNSGAG AGCATTCTTA AAAATCTCCT GC - #C                53                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:123:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 53 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:123:                      - - GCGCGCCTGC AGAATGCATC AGCAATTNNS AGCATTCTTA AAAATCTCCT GC - #C                53                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:124:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 53 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:124:                      - - GCGCGCCTGC AGAATGCATC AGCAATTGAG NNSATTCTTA AAAATCTCCT GC - #C                53                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:125:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 71 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:125:                      - - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCNNSCTTA AAAATCTCCT GC -             #CATGTCTG     60                                                                 - - CCGCTAGCCA C               - #                  - #                      - #       71                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:126:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 71 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:126:                      - - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTNNSA AAAATCTCCT GC -             #CATGTCTG     60                                                                 - - CCGCTAGCCA C               - #                  - #                      - #       71                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:127:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 71 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:127:                      - - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTCTTN NSAATCTCCT GC -             #CATGTCTG     60                                                                 - - CCGCTAGCCA C               - #                  - #                      - #       71                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:128:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 134 amino - #acids                                                (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:128:                      - -      Met Ala Pro Met Thr Gln Thr Thr - # Ser Leu Lys Thr Ser Trp        Val Asn                                                                              1             - #  5                - #   10               - #         15                                                                               - -      Cys Ser Asn Met Ile Asp Glu Ile - # Ile Thr His Leu Lys Gln       Pro Pro                                                                                          20 - #                 25 - #                 30             - -      Leu Pro Leu Leu Asp Phe Asn Asn - # Leu Asn Gly Glu Asp Gln        Asp Ile                                                                                      35     - #             40     - #             45                  - -      Leu Met Glu Asn Asn Leu Arg Arg - # Pro Asn Leu Glu Ala Phe       Asn Arg                                                                                  50         - #         55         - #         60                      - -      Ala Val Lys Ser Leu Gln Asn Ala - # Ser Ala Ile Glu Ser Ile       Leu Lys                                                                              65             - #     70             - #     75             - #         80                                                                            - -      Asn Leu Leu Pro Cys Leu Pro Leu - # Ala Thr Ala Ala Pro Thr        Arg His                                                                                           - #   85               - #   90               - #         95                                                                               - -      Pro Ile His Ile Lys Asp Gly Asp - # Trp Asn Glu Phe Arg Arg       Lys Leu                                                                                          100 - #                105 - #                110            - -      Thr Phe Tyr Leu Lys Thr Leu Glu - # Asn Ala Gln Ala Gln Gln        Thr Thr                                                                                      115     - #            120     - #            125                 - -      Leu Ser Leu Ala Ile Phe                                                      130                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:129:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 133 amino - #acids                                                (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 1                                                               (D) OTHER INFORMATION: - #/note= "Met- may or may not precede                     the amino - # acid in position 1"                               - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 18                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 18 is Asn                        or Ile"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 25                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 25 is Thr                        or His"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 29                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 29 is Gln,                       Arg, or - #Val"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 32                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 32 is Leu,                       Ala, or - #Asn"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 37                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 37 is Phe,                       Pro, or - #Ser"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 42                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 42 is Glu,                       Ala, or - #Ser"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 45                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 45 is Gln,                       Val, or - #Met"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 51                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 51 is Asn                        or Arg"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 55                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 55 is Arg,                       Leu, or - #Thr"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 59                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 59 is Glu                        or Leu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 60                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 60 is Ala                        or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 62                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 62 is Asn                        or Val"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 67                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 67 is Ser,                       Asn, or - #His"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 69                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 69 is Gln                        or Glu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 73                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 73 is Ala                        or Gly"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 76                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 76 is Ser                        or Ala"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 79                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 79 is Lys                        or Arg"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 82                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 82 is Leu,                       Glu, or - #Val"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 87                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 87 is Leu                        or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 93                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 93 is Pro                        or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 98                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 98 is His,                       Ile, or - #Thr"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 101                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 101 is Asp                       or Ala"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 105                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 105 is Asn                       or Glu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 109                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 109 is Arg                       or Glu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 116                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 116 is Lys                       or Val"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 120                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 120 is Asn,                      Gln, or - #His"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 123                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 123 is Ala                       or Glu"                                                         - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:129:                      - -      Ala Pro Met Thr Gln Thr Thr Ser - # Leu Lys Thr Ser Trp Val        Asn Cys                                                                              1             - #  5                - #   10               - #         15                                                                               - -      Ser Xaa Met Ile Asp Glu Ile Ile - # Xaa His Leu Lys Xaa Pro       Pro Xaa                                                                                          20 - #                 25 - #                 30             - -      Pro Leu Leu Asp Xaa Asn Asn Leu - # Asn Xaa Glu Asp Xaa Asp        Ile Leu                                                                                      35     - #             40     - #             45                  - -      Met Glu Xaa Asn Leu Arg Xaa Pro - # Asn Leu Xaa Xaa Phe Xaa       Arg Ala                                                                                  50         - #         55         - #         60                      - -      Val Lys Xaa Leu Xaa Asn Ala Ser - # Xaa Ile Glu Xaa Ile Leu       Xaa Asn                                                                              65             - #     70             - #     75             - #         80                                                                            - -      Leu Xaa Pro Cys Leu Pro Xaa Ala - # Thr Ala Ala Pro Xaa Arg        His Pro                                                                                           - #   85               - #   90               - #         95                                                                               - -      Ile Xaa Ile Lys Xaa Gly Asp Trp - # Xaa Glu Phe Arg Xaa Lys       Leu Thr                                                                                          100 - #                105 - #                110            - -      Phe Tyr Leu Xaa Thr Leu Glu Xaa - # Ala Gln Xaa Gln Gln Thr        Thr Leu                                                                                      115     - #            120     - #            125                 - -      Ser Leu Ala Ile Phe                                                          130                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:130:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 111 amino - #acids                                                (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 1                                                               (D) OTHER INFORMATION: - #/note= "Met- or Met-Ala may or may                      not prece - #de the amino acid in position 1"                   - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 4                                                               (D) OTHER INFORMATION: - #/note= "Xaa at position 4 is Asn or                      Ile"                                                            - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 11                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 11 is Thr                        or His"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 15                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 15 is Gln,                       Arg, or - #Val"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 18                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 18 is Leu,                       Ala, or - #Asn"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY:  Modified - #-site                                              (B) LOCATION: 23                                                              (C) OTHER INFORMATION: - #/note= "Xaa at position 23 is Phe,                       Pro, or - #Ser"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 28                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 28 is Glu,                       Ala, or - #Ser"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 31                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 31 is Gln,                       Val, or - #Met"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 37                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 37 is Asn                        or Arg"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 41                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 41 is Arg,                       Leu, or - #Thr"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 45                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 45 is Glu                        or Leu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 46                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 46 is Ala                        or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 48                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 48 is Asn                        or Val"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 53                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 53 is Ser,                       Asn, or - #His"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 55                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 55 is Gln                        or Glu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 59                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 59 is Ala                        or Gly"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 62                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 62 is Ser                        or Ala"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 65                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 65 is Lys                        or Arg"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 68                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 68 is Leu,                       Glu, or - #Val"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 73                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 73 is Leu                        or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 79                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 79 is Pro                        or Ser"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 84                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 84 is His,                       Ile, or - #Thr"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 87                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 87 is Asp                        or Ala"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 91                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 91 is Asn                        or Glu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 95                                                              (D) OTHER INFORMATION: - #/note= "Xaa at position 95 is Arg                        or Glu"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 102                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 102 is Lys                       or Val"                                                         - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 106                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 106 is Asn,                      Gln, or - #His"                                                 - -     (ix) FEATURE:                                                                  (A) NAME/KEY: Modified-sit - #e                                               (B) LOCATION: 109                                                             (D) OTHER INFORMATION: - #/note= "Xaa at position 109 is Ala                       or Glu"                                                         - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:130:                      - -      Asn Cys Ser Xaa Met Ile Asp Glu - # Ile Ile Xaa His Leu Lys        Xaa Pro                                                                              1             - #  5                - #   10               - #         15                                                                               - -      Pro Xaa Pro Leu Leu Asp Xaa Asn - # Asn Leu Asn Xaa Glu Asp       Xaa Asp                                                                                          20 - #                 25 - #                 30             - -      Ile Leu Met Glu Xaa Asn Leu Arg - # Xaa Pro Asn Leu Xaa Xaa        Phe Xaa                                                                                      35     - #             40     - #             45                  - -      Arg Ala Val Lys Xaa Leu Xaa Asn - # Ala Ser Xaa Ile Glu Xaa       Ile Leu                                                                                  50         - #         55         - #         60                      - -      Xaa Asn Leu Xaa Pro Cys Leu Pro - # Xaa Ala Thr Ala Ala Pro       Xaa Arg                                                                              65             - #     70             - #     75             - #         80                                                                            - -      His Pro Ile Xaa Ile Lys Xaa Gly - # Asp Trp Xaa Glu Phe Arg        Xaa Lys                                                                                           - #   85               - #   90               - #         95                                                                               - -      Leu Thr Phe Tyr Leu Xaa Thr Leu - # Glu Xaa Ala Gln Xaa Gln       Gln                                                                                              100 - #                105 - #                110            - -  - - (2) INFORMATION FOR SEQ ID NO:131:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 58 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:131:                      - - CTAGCCACGG CCGCACCCAC GCGACATCCA ATCCATATCA AGGACGGTGA CT - #GGAATG           58                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:132:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 58 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:132:                      - - TTAACATTCC AGTCACCGTC CTTGATATGG ATTGGATGTC GCGTGGGTGC GG - #CCGTGG           58                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:133:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 29 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: double                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (genomic)                                     - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:133:                      - - AAGGAGATAT ATCCATGAAC TGCTCTAAC         - #                  - #                29                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:134:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 5 amino - #acids                                                  (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:134:                      - -      Met Asn Cys Ser Asn                                                      1             - #  5                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:135:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 120 amino - #acids                                                (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:135:                      - -      Met Asn Cys Ser Asn Met Ile Asp - # Glu Ile Ile Thr His Leu        Lys Gln                                                                              1             - #  5                - #   10               - #         15                                                                               - -      Pro Pro Leu Pro Leu Leu Asp Phe - # Asn Asn Leu Asn Gly Glu       Asp Gln                                                                                          20 - #                 25 - #                 30             - -      Asp Ile Leu Met Glu Asn Asn Leu - # Arg Arg Pro Asn Leu Glu        Ala Phe                                                                                      35     - #             40     - #             45                  - -      Asn Arg Ala Val Lys Ser Leu Gln - # Asn Ala Ser Ala Ile Glu       Ser Ile                                                                                  50         - #         55         - #         60                      - -      Leu Lys Asn Leu Leu Pro Cys Leu - # Pro Leu Ala Thr Ala Ala       Pro Thr                                                                              65             - #     70             - #     75             - #         80                                                                            - -      Arg His Pro Ile His Ile Lys Asp - # Gly Asp Trp Asn Glu Phe        Arg Arg                                                                                           - #   85               - #   90               - #         95                                                                               - -      Lys Leu Thr Phe Tyr Leu Lys Thr - # Leu Glu Asn Ala Gln Ala       Gln Gln                                                                                          100 - #                105 - #                110            - -      Thr Thr Leu Arg Leu Ala Ile Phe                                                  115     - #            120                                        - -  - - (2) INFORMATION FOR SEQ ID NO:136:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 71 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:136:                      - - AATTCCGTCG TAAACTGACC TTCTATCTGA AAACCTTGGA GAACGCGCAG GC -             #TCAACAGA     60                                                                 - - CCACTCTGTC G               - #                  - #                      - #       71                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:137:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 71 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:137:                      - - CTAGCGACAG AGTGGTCTGT TGAGCCTGCG CGTTCTCCAA GGTTTTCAGA TA -             #GAAGGTCA     60                                                                 - - GTTTACGACG G               - #                  - #                      - #       71                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:138:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 71 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:138:                      - - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTCTTA AANNSCTCCT GC -             #CATGTCTG     60                                                                 - - CCGCTAGCCA C               - #                  - #                      - #       71                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:139:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 71 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:139:                      - - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTCTTA AAAATNNSCT GC -             #CATGTCTG     60                                                                 - - CCGCTAGCCA C               - #                  - #                      - #       71                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:140:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 71 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:140:                      - - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTCTTA AAAATCTCNN SC -             #CATGTCTG     60                                                                 - - CCGCTAGCCA C               - #                  - #                      - #       71                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:141:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 89 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:141:                      - - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTCTTA AAAATCTCCT GN -             #NSTGTCTG     60                                                                 - - CCGCTAGCCA CGGCCGCACC CACGCGACA         - #                  - #                89                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:142:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 89 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:142:                      - - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTCTTA AAAATCTCCT GC -             #CANNSCTG     60                                                                 - - CCGCTAGCCA CGGCCGCACC CACGCGACA         - #                  - #                89                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:143:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 89 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:143:                      - - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTCTTA AAAATCTCCT GC -             #CATGTNNS     60                                                                 - - CCGCTAGCCA CGGCCGCACC CACGCGACA         - #                  - #                89                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:144:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 408 base - #pairs                                                 (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: double                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (genomic)                                     - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:144:                      - - ATGGCTCCAA TGACTCAGAC TACTTCTCTT AAGACTTCTT GGGTTAACTG CT -             #CTAACATG     60                                                                 - - ATCGATGAAA TTATAACACA CTTAAAGCAG CCACCTTTGC CTTTGCTGGA CT -            #TCAACAAC    120                                                                 - - CTCAATGGGG AAGACCAAGA CATTCTGATG GAAAATAACC TTCGAAGGCC AA -            #ACCTGGAG    180                                                                 - - GCATTCAACA GGGCTGTCAA GAGTTTACAG AATGCATCAG CAATTGAGAG CA -            #TTCTTAAA    240                                                                 - - AATCTCCTGC CATGTCTGCC CCTGGCCACG GCCGCACCCA CGCGACATCC AA -            #TCCATATC    300                                                                 - - AAGGACGGTG ACTGGAATGA ATTCCGTCGT AAACTGACCT TCTATCTGAA AA -            #CCTTGGAG    360                                                                 - - AACGCGCAGG CTCAACAGAC CACTCTGTCG CTAGCGATCT TTTAATAA  - #                   408                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:145:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 157 base - #pairs                                                 (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: double                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (genomic)                                     - -     (ix) FEATURE:                                                                  (A) NAME/KEY: CDS                                                             (B) LOCATION: 1..156                                                 - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:145:                      - - ATC GAT GAA ATC ATC ACC CAC CTG AAG CAG CC - #A CCG CTG CCG CTG CTG           48                                                                       Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pr - #o Pro Leu Pro Leu Leu             1               5 - #                 10 - #                 15              - - GAC TTC AAC AAC CTC AAT GGT GAA GAC CAA GA - #T ATC CTG ATG GAA AAT           96                                                                       Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln As - #p Ile Leu Met Glu Asn                        20     - #             25     - #             30                  - - AAC CTT CGT CGT CCA AAC CTC GAG GCA TTC AA - #C CGT GCT GTC AAG TCT          144                                                                       Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe As - #n Arg Ala Val Lys Ser                    35         - #         40         - #         45                      - - CTG CAG AAT GCA T           - #                  - #                      - #     157                                                                  Leu Gln Asn Ala                                                                    50                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:146:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 52 amino - #acids                                                 (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: protein                                           - -           (xi) SEQUENCE DESCRIPTION: - # SEQ ID NO:146:                   - - Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pr - #o Pro Leu Pro Leu Leu        1               5 - #                 10 - #                 15              - - Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln As - #p Ile Leu Met Glu Asn                   20     - #             25     - #             30                  - - Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe As - #n Arg Ala Val Lys Ser               35         - #         40         - #         45                      - - Leu Gln Asn Ala                                                               50                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:147:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 414 base - #pairs                                                 (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: double                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (genomic)                                     - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:147:                      - - CCATGGCTCC AATGACTCAG ACTACTTCTC TTAAGACTTC TTGGGTTAAC TG -             #CTCTAACA     60                                                                 - - TGATCGATGA AATTATAACA CACTTAAAGC AGCCACCTTT GCCTTTGCTG GA -            #CTTCAACA    120                                                                 - - ACCTCAATGG GGAAGACCAA GACATTCTGA TGGAAAATAA CCTTCGAAGG CC -            #AAACCTGG    180                                                                 - - AGGCATTCAA CAGGGCTGTC AAGAGTTTAC AGAATGCATC AGCAATTGAG AG -            #CATTCTTA    240                                                                 - - AAAATCTCCT GCCATGTCTG CCCCTGGCCA CGGCCGCACC CACGCGACAT CC -            #AATCCATA    300                                                                 - - TCAAGGACGG TGACTGGAAT GAATTCCGTC GTAAACTGAC CTTCTATCTG AA -            #AACCTTGG    360                                                                 - - AGAACGCGCA GGCTCAACAG ACCACTCTGT CGCTAGCGAT CTTTTAATAA GC - #TT              414                                                                       - -  - - (2) INFORMATION FOR SEQ ID NO:148:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 414 base - #pairs                                                 (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: double                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (genomic)                                     - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:148:                      - - AAGCTTATTA AAAGATCGCT AGCGACAGAG TGGTCTGTTG AGCCTGCGCG TT -             #CTCCAAGG     60                                                                 - - TTTTCAGATA GAAGGTCAGT TTACGACGGA ATTCATTCCA GTCACCGTCC TT -            #GATATGGA    120                                                                 - - TTGGATGTCG CGTGGGTGCG GCCGTGGCCA GGGGCAGACA TGGCAGGAGA TT -            #TTTAAGAA    180                                                                 - - TGCTCTCAAT TGCTGATGCA TTCTGTAAAC TCTTGACAGC CCTGTTGAAT GC -            #CTCCAGGT    240                                                                 - - TTGGCCTTCG AAGGTTATTT TCCATCAGAA TGTCTTGGTC TTCCCCATTG AG -            #GTTGTTGA    300                                                                 - - AGTCCAGCAA AGGCAAAGGT GGCTGCTTTA AGTGTGTTAT AATTTCATCG AT -            #CATGTTAG    360                                                                 - - AGCAGTTAAC CCAAGAAGTC TTAAGAGAAG TAGTCTGAGT CATTGGAGCC AT - #GG              414                                                                       - -  - - (2) INFORMATION FOR SEQ ID NO:149:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 81 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: double                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (genomic)                                     - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:149:                      - - ATGATGATTA CTCTGCGCAA ACTTCCTCTG GCGGTTGCCG TCGCAGCGGG CG -             #TAATGTCT     60                                                                 - - GCTCAGGCCA TGGCTAACTG C           - #                  - #                      - #81                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:150:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 81 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: double                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (genomic)                                     - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:150:                      - - GCAGTTAGCC ATGGCCTGAG CAGACATTAC GCCCGCTGCG ACGGCAACCG CC -             #AGAGGAAG     60                                                                 - - TTTGCGCAGA GTAATCATCA T           - #                  - #                      - #81                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:151:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:151:                      - - CATGGCTAAC TGCTCTAACA TGAT          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:152:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 22 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:152:                      - - CGATCATGTT AGAGCAGTTA GC           - #                  - #                     22                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:153:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 12 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: double                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (genomic)                                     - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:153:                      - - ATGGCTAACT GC              - #                  - #                      - #       12                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:154:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 4 amino - #acids                                                  (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:154:                      - -      Met Ala Asn Cys                                                          1                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:155:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 34 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:155:                      - - GCCGATACCG CGGCATACTC CCACCATTCA GAGA       - #                  -      #        34                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:156:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 33 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:156:                      - - GCCGATAAGA TCTAAAACGG GTATGGAGAA ACA       - #                  -      #         33                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:157:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 89 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:157:                      - - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTCTTA AAAATCTCCT GC -            #CATGTCTG     60                                                                 - - NNSCTAGCCA CGGCCGCACC CACGCGACA         - #                  - #                89                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:158:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 89 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:158:                      - - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTCTTA AAAATCTCCT GC -             #CATGTCTG     60                                                                 - - CCGNNSGCCA CGGCCGCACC CACGCGACA         - #                  - #                89                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:159:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 89 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:159:                      - - GCGCGCCTGC AGAATGCATC AGCAATTGAG AGCATTCTTA AAAATCTCCT GC -             #CATGTCTG     60                                                                 - - CCGCTANNSA CGGCCGCACC CACGCGACA         - #                  - #                89                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:160:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 86 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:160:                      - - CGCGCGGAAT TCATTCCAGT CACCGTCCTT GATATGGATT GGATGTCGCG TG -             #GGTGCGGC     60                                                                 - - SNNGGCCAGG GGCAGACATG GCAGGA          - #                  - #                  86                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:161:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 86 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:161:                      - - CGCGCGGAAT TCATTCCAGT CACCGTCCTT GATATGGATT GGATGTCGCG TG -             #GGTGCSNN     60                                                                 - - CGTGGCCAGG GGCAGACATG GCAGGA          - #                  - #                  86                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:162:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 86 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:162:                      - - CGCGCGGAAT TCATTCCAGT CACCGTCCTT GATATGGATT GGATGTCGCG TG -             #GGSNNGGC     60                                                                 - - CGTGGCCAGG GGCAGACATG GCAGGA          - #                  - #                  86                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:163:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 86 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:163:                      - - CGCGCGGAAT TCATTCCAGT CACCGTCCTT GATATGGATT GGATGTCGCG TS -             #NNTGCGGC     60                                                                 - - CGTGGCCAGG GGCAGACATG GCAGGA          - #                  - #                  86                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:164:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 86 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:164:                      - - CGCGCGGAAT TCATTCCAGT CACCGTCCTT GATATGGATT GGATGTCGSN NG -             #GGTGCGGC     60                                                                 - - CGTGGCCAGG GGCAGACATG GCAGGA          - #                  - #                  86                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:165:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 48 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:165:                      - - TTTCAGATAG AAGGTCAGTT TACGACGGAA SNNATTCCAG TCACCGTC  - #                    48                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:166:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 48 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:166:                      - - TTTCAGATAG AAGGTCAGTT TACGACGSNN TTCATTCCAG TCACCGTC  - #                    48                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:167:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 48 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:167:                      - - TTTCAGATAG AAGGTCAGTT TACGSNNGAA TTCATTCCAG TCACCGTC  - #                    48                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:168:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 48 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:168:                      - - TTTCAGATAG AAGGTCAGTT TSNNACGGAA TTCATTCCAG TCACCGTC  - #                    48                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:169:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 48 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:169:                      - - TTTCAGATAG AAGGTCAGSN NACGACGGAA TTCATTCCAG TCACCGTC  - #                    48                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:170:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 48 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:170:                      - - TTTCAGATAG AAGGTSNNTT TACGACGGAA TTCATTCCAG TCACCGTC  - #                    48                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:171:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 23 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:171:                      - - CGCGCGAAGC TTATTACTGT TGA           - #                  - #                    23                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:172:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 78 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:172:                      - - CGCGCGAAGC TTATTACTGT TGAGCCTGCG CGTTCTCCAA GGTTTTCAGA TA -             #GAASNNCA     60                                                                 - - GTTTACGACG GAATTCAT             - #                  - #                      - #  78                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:173:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 78 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:173:                      - - CGCGCGAAGC TTATTACTGT TGAGCCTGCG CGTTCTCCAA GGTTTTCAGA TA -             #SNNGGTCA     60                                                                 - - GTTTACGACG GAATTCAT             - #                  - #                      - #  78                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:174:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 78 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:174:                      - - CGCGCGAAGC TTATTACTGT TGAGCCTGCG CGTTCTCCAA GGTTTTCAGS NN -             #GAAGGTCA     60                                                                 - - GTTTACGACG GAATTCAT             - #                  - #                      - #  78                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:175:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 78 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:175:                      - - CGCGCGAAGC TTATTACTGT TGAGCCTGCG CGTTCTCCAA GGTTTTSNNA TA -             #GAAGGTCA     60                                                                 - - GTTTACGACG GAATTCAT             - #                  - #                      - #  78                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:176:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 78 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:176:                      - - CGCGCGAAGC TTATTACTGT TGAGCCTGCG CGTTCTCCAA GGTSNNCAGA TA -             #GAAGGTCA     60                                                                 - - GTTTACGACG GAATTCAT             - #                  - #                      - #  78                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:177:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 78 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:177:                      - - CGCGCGAAGC TTATTACTGT TGAGCCTGCG CGTTCTCCAA SNNTTTCAGA TA -             #GAAGGTCA     60                                                                 - - GTTTACGACG GAATTCAT             - #                  - #                      - #  78                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:178:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 60 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:178:                      - - CGCGCGAAGC TTATTACTGT TGAGCCTGCG CGTTCTCSNN GGTTTTCAGA TA -             #GAAGGTCA     60                                                                 - -  - - (2) INFORMATION FOR SEQ ID NO:179:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 60 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:179:                      - - CGCGCGAAGC TTATTACTGT TGAGCCTGCG CGTTSNNCAA GGTTTTCAGA TA -            #GAAGGTCA     60                                                                 - -  - - (2) INFORMATION FOR SEQ ID NO:180:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 60 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:180:                      - - CGCGCGAAGC TTATTACTGT TGAGCCTGCG CSNNCTCCAA GGTTTTCAGA TA -            #GAAGGTCA     60                                                                 - -  - - (2) INFORMATION FOR SEQ ID NO:181:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 60 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:181:                      - - CGCGCGAAGC TTATTACTGT TGAGCCTGSN NGTTCTCCAA GGTTTTCAGA TA -            #GAAGGTCA     60                                                                 - -  - - (2) INFORMATION FOR SEQ ID NO:182:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 60 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:182:                      - - CGCGCGAAGC TTATTACTGT TGAGCSNNCG CGTTCTCCAA GGTTTTCAGA TA -            #GAAGGTCA     60                                                                 - -  - - (2) INFORMATION FOR SEQ ID NO:183:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 60 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:183:                      - - CGCGCGAAGC TTATTACTGT TGSNNCTGCG CGTTCTCCAA GGTTTTCAGA TA -            #GAAGGTCA     60                                                                 - -  - - (2) INFORMATION FOR SEQ ID NO:184:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:184:                      - - TGCTCTAACA TGATCGATGA AATT          - #                  - #                    24                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:185:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:185:                      - - GAAATTATAA CACACTTAAA GCAG          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:186:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:186:                      - - AAGCAGCCAC CTTTGCCTTT GCTG          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:187:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:187:                      - - AAGCAGCCAC CGCTGCCGCT GCTG          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:188:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:188:                      - - CTCAATGGTG AAGACCAAGA TATC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:189:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:189:                      - - GATATCCTGA TGGAAAATAA CCTT          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:190:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:190:                      - - AACCTTCGTC GTCCAAACCT CGAG          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:191:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:191:                      - - CTCGAGGCAT TCAACCGTGC TGTC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:192:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:192:                      - - GCTGTCAAGT CTCTGCAGAA TGCA          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:193:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:193:                      - - AATGCATCAG CAATTGAGAG CATT          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:194:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:194:                      - - AGCATTCTTA AAAATCTCCT GCCA          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:195:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:195:                      - - CTGCCATGTC TGCCCCTGGC CACG          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:196:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:196:                      - - CTGGCCACGG CCGCACCCAC GCGA          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:197:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:197:                      - - AATGAATTCC GTCGTAAACT GACC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:198:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:198:                      - - CTGACCTTCT ATCTGAAAAC CTTG          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:199:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:199:                      - - ACCTTGGAGA ACGCGCAGGC TCAA          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:200:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 22 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:200:                      - - GAATGCATCA GCAATTGAGA GC           - #                  - #                     22                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:201:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 20 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:201:                      - - AATTGCTGAT GCATTCTGCA            - #                  - #                      - # 20                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:202:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:202:                      - - ATTCTTAAAA ATCTCCTGCC ATGT          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:203:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:203:                      - - CAGGAGATTT TTAAGAATGC TCTC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:204:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 30 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:204:                      - - CTGCCCCTGG CCACGGCCGC ACCCACGCGA         - #                  - #               30                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:205:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 30 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:205:                      - - GGGTGCGGCC GTGGCCAGGG GCAGACATGG         - #                  - #               30                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:206:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 34 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:206:                      - - CATCCAATCA TCATCCGTGA CGGTGACTGG AATG       - #                  -      #        34                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:207:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 44 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:207:                      - - AATTCATTCC AGTCACCGTC ACGGATGATG ATTGGATGTC GCGT   - #                      - # 44                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:208:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 34 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:208:                      - - CGCCCAATCA TCATCCGTGA CGGTGACTGG AATG       - #                  -      #        34                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:209:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 44 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:209:                      - - AATTCATTCC AGTCACCGTC ACGGATGATG ATTGGGCGTC GCGT   - #                      - # 44                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:210:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 40 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:210:                      - - CATGGCTAAC TGCTCTAACA TGATCGATGA AATTATAACA     - #                      - #    40                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:211:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 45 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:211:                      - - CTTTAAGTGT GTTATAATTT CATCGATCAT GTTAGAGCAG TTAGC   - #                      - #45                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:212:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:212:                      - - CACTTAAAGC AGCCACCTTT GCCTTTGCTG GACTTC      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:213:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:213:                      - - GAGGTTGTTG AAGTCCAGCA AAGGCAAAGG TGGCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:214:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:214:                      - - AACAACCTCA ATGACGAAGA CATGTCT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:215:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:215:                      - - AGACATGTCT TCGTCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:216:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 339 base - #pairs                                                 (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: double                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (genomic)                                     - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:216:                      - - ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA GC -             #CACCGCTG     60                                                                 - - CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG ATATCCTGAT GG -            #AAAATAAC    120                                                                 - - CTTCGTCGTC CAAACCTCGA GGCATTCAAC CGTGCTGTCA ACTCTCTGCA GA -            #ATGCATCA    180                                                                 - - GCAATTGAGA GCATTCTTAA AAATCTCCTG CCATGTCTGC CCCTGGCCAC GG -            #CCGCACCC    240                                                                 - - ACGCGACATC CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TA -            #AACTGACC    300                                                                 - - TTCTATCTGA AAACCTTGGA GAACGCGCAG GCTCAACAG      - #                      - #   339                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:217:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 111 amino - #acids                                                (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:217:                      - -      Asn Cys Ser Asn Met Ile Asp Glu - # Ile Ile Thr His Leu Lys        Gln Pro                                                                              1             - #  5                - #   10               - #         15                                                                               - -      Pro Leu Pro Leu Leu Asp Phe Asn - # Asn Leu Asn Gly Glu Asp       Gln Asp                                                                                          20 - #                 25 - #                 30             - -      Ile Leu Met Glu Asn Asn Leu Arg - # Arg Pro Asn Leu Glu Ala        Phe Asn                                                                                      35     - #             40     - #             45                  - -      Arg Ala Val Lys Ser Leu Gln Asn - # Ala Ser Ala Ile Glu Ser       Ile Leu                                                                                  50         - #         55         - #         60                      - -      Lys Asn Leu Leu Pro Cys Leu Pro - # Leu Ala Thr Ala Ala Pro       Thr Arg                                                                              65             - #     70             - #     75             - #         80                                                                            - -      His Pro Ile His Ile Lys Asp Gly - # Asp Trp Asn Glu Phe Arg        Arg Lys                                                                                           - #   85               - #   90               - #         95                                                                               - -      Leu Thr Phe Tyr Leu Trp Thr Leu - # Glu Asn Ala Gln Ala Gln       Gln                                                                                              100 - #                105 - #                110            - -  - - (2) INFORMATION FOR SEQ ID NO:218:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 111 amino - #acids                                                (B) TYPE: amino acid                                                          (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: peptide                                           - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:218:                      - -      Asn Cys Ser Asn Met Ile Asp Glu - # Ile Ile Thr His Leu Lys        Gln Pro                                                                              1             - #  5                - #   10               - #         15                                                                               - -      Pro Leu Pro Leu Leu Asp Phe Asn - # Asn Leu Asn Gly Glu Asp       Gln Asp                                                                                          20 - #                 25 - #                 30             - -      Ile Leu Met Asp Asn Asn Leu Arg - # Arg Pro Asn Leu Glu Ala        Phe Asn                                                                                      35     - #             40     - #             45                  - -      Arg Ala Val Lys Ser Leu Gln Asn - # Ala Ser Ala Ile Glu Ser       Ile Leu                                                                                  50         - #         55         - #         60                      - -      Lys Asn Leu Leu Pro Cys Leu Pro - # Leu Ala Thr Ala Ala Pro       Thr Arg                                                                              65             - #     70             - #     75             - #         80                                                                            - -      His Pro Ile His Ile Lys Asp Gly - # Asp Trp Asn Glu Phe Arg        Arg Lys                                                                                           - #   85               - #   90               - #         95                                                                               - -      Leu Thr Phe Tyr Leu Lys Thr Leu - # Glu Asn Ala Gln Ala Gln       Gln                                                                                              100 - #                105 - #                110            - -  - - (2) INFORMATION FOR SEQ ID NO:219:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 45 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:219:                      - - CTTTAAGTGT GTTATAATTT CTTCGATCAT GTTAGAGCAG TTAGC   - #                      - #45                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:220:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 339 base - #pairs                                                 (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: double                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (genomic)                                     - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:220:                      - - ATGGCTAACT GCTCTAACAT GATCGATGAA ATCATCACCC ACCTGAAGCA GC -             #CACCGCTG     60                                                                 - - CCGCTGCTGG ACTTCAACAA CCTCAATGGT GAAGACCAAG ATATCCTGAT GG -            #AAAATAAC    120                                                                 - - CTTCGTCGTC CAAACCTCGA GGCATTCAAC CGTGCTGTCA ACTCTCTGCA GA -            #ATGCATCA    180                                                                 - - GCAATTGAGA GCATTCTTAA AAATCTCCTG CCATGTCTGC CCCTGGCCAC GG -            #CCGCACCC    240                                                                 - - ACGCGACATC CAATCCATAT CAAGGACGGT GACTGGAATG AATTCCGTCG TA -            #AACTGACC    300                                                                 - - TTCTATCTGT GGACCTTGGA GAACGCGCAG GCTCAACAG      - #                      - #   339                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:221:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 40 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:221:                      - - CATGGCTAAC TGCTCTAACA TGATCAACGA AATTATAACA     - #                      - #    40                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:222:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 58 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:222:                      - - CGCGCGCCAT GGCTAACTGC TCTNNSATGA TCGATGAAAT TATAACACAC TT - #AAAGCA           58                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:223:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 58 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:223:                      - - CGCGCGCCAT GGCTAACTGC TCTAACNNSA TCGATGAAAT TATAACACAC TT - #AAAGCA           58                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:224:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 58 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:224:                      - - CGCGCGCCAT GGCTAACTGC TCTAACATGN NSGATGAAAT TATAACACAC TT - #AAAGCA           58                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:225:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 58 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:225:                      - - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCNNSGAAAT TATAACACAC TT - #AAAGCA           58                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:226:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 58 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:226:                      - - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATNNSAT TATAACACAC TT - #AAAGCA           58                                                                        - -  - - (2) INFORMATION FOR SEQ ID NO:227:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 76 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:227:                      - - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAANN SATAACACAC TT -             #AAAGCAGC     60                                                                 - - CACCTTTGCC TTTGCT             - #                  - #                      - #    76                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:228:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 76 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:228:                      - - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TNNSACACAC TT -             #AAAGCAGC     60                                                                 - - CACCTTTGCC TTTGCT             - #                  - #                      - #    76                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:229:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 76 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:229:                      - - CGCGCGCCAT GGCTAACTGC TCTAACATGA TCGATGAAAT TATANNSCAC TT -             #AAAGCAGC     60                                                                 - - CACCTTTGCC TTTGCT             - #                  - #                      - #    76                                                                  - -  - - (2) INFORMATION FOR SEQ ID NO:230:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 40 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:230:                      - - CATGGCTAAC TGCTCTAACA TGATCAGCGA AATTATAACA     - #                      - #    40                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:231:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 45 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:231:                      - - CTTTAAGTGT GTTATAATTT CGCTGATCAT GTTAGAGCAG TTAGC   - #                      - #45                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:232:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 40 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:232:                      - - CATGGCTAAC TGCTCTAACA TGATCACCGA AATTATAACA     - #                      - #    40                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:233:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 45 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:233:                      - - CTTTAAGTGT GTTATAATTT CCGTGATCAT GTTAGAGCAG TTAGC   - #                      - #45                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:234:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 40 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:234:                      - - CATGGCTAAC TGCTCTAACA TGATCGATAA CATTATAACA     - #                      - #    40                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:235:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 45 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:235:                      - - CTTTAAGTGT GTTATAATGT TATCGATCAT GTTAGAGCAG TTAGC   - #                      - #45                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:236:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 40 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:236:                      - - CATGGCTAAC TGCTCTAACA TGATCGATGA CATTATAACA     - #                      - #    40                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:237:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 45 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:237:                      - - CTTTAAGTGT GTTATAATGT CATCGATCAT GTTAGAGCAG TTAGC   - #                      - #45                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:238:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 40 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:238:                      - - CATGGCTAAC TGCTCTAACA TGATCGATCA GATTATAACA     - #                      - #    40                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:239:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 45 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:239:                      - - CTTTAAGTGT GTTATAATCT GATCGATCAT GTTAGAGCAG TTAGC   - #                      - #45                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:240:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 40 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:240:                      - - CATGGCTAAC TGCTCTAACA TGATCGATCT GATTATAACA     - #                      - #    40                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:241:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 45 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:241:                      - - CTTTAAGTGT GTTATAATCA GATCGATCAT GTTAGAGCAG TTAGC   - #                      - #45                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:242:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 40 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:242:                      - - CATGGCTAAC TGCTCTAACA TGATCGATGT TATTATAACA     - #                      - #    40                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:243:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 45 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:243:                      - - CTTTAAGTGT GTTATAATAA CATCGATCAT GTTAGAGCAG TTAGC   - #                      - #45                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:244:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:244:                      - - CACTTAAAGC AGCCACCTTT GCCTGCTCTG GACTTC      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:245:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:245:                      - - GAGGTTGTTG AAGTCCAGAG CAGGCAAAGG TGGCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:246:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:246:                      - - CACTTAAAGC AGCCACCTTT GCCTCGTCTG GACTTC      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:247:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:247:                      - - GAGGTTGTTG AAGTCCAGAC GAGGCAAAGG TGGCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:248:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:248:                      - - CACTTAAAGC AGCCACCTTT GCCTCAGCTG GACTTC      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:249:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:249:                      - - GAGGTTGTTG AAGTCCAGCT GAGGCAAAGG TGGCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:250:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:250:                      - - CACTTAAAGC AGCCACCTTT GCCTGAACTG GACTTC      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:251:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:251:                      - - GAGGTTGTTG AAGTCCAGCT CAGGCAAAGG TGGCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:252:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:252:                      - - CACTTAAAGC AGCCACCTTT GCCTATCCTG GACTTC      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:253:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:253:                      - - GAGGTTGTTG AAGTCCAGGA TAGGCAAAGG TGGCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:254:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:254:                      - - CACTTAAAGC AGCCACCTTT CCCTTTCCTG GACTTC      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:255:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:255:                      - - GAGGTTGTTG AAGTCCAGGA AAGGCAAAGG TGGCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:256:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:256:                      - - CACTTAAAGC AGCCACCTTT GCCTACCCTG GACTTC      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:257:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:257:                      - - GAGGTTGTTG AAGTCCAGGG TAGGCAAAGG TGGCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:258:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:258:                      - - AACAACCTCA ATCGTGAAGA CCAAGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:259:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:259:                      - - ATCTTGGTCT TCACGATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:260:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:260:                      - - AACAACCTCA ATAACGAAGA CCAAGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:261:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:261:                      - - ATCTTGGTCT TCGTTATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:262:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:262:                      - - AACAACCTCA ATGAAGAAGA CCAAGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:263:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:263:                      - - ATCTTGGTCT TCTTCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:264:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:264:                      - - AACAACCTCA ATATCGAAGA CCAAGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:265:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:265:                      - - ATCTTGGTCT TCGATATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:266:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:266:                      - - AACAACCTCA ATCTGGAAGA CCAAGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:267:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:267:                      - - ATCTTGGTCT TCCAGATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:268:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:268:                      - - AACAACCTCA ATAAAGAAGA CCAAGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:269:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:269:                      - - ATCTTGGTCT TCTTTATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:270:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:270:                      - - AACAACCTCA ATATGGAAGA CCAAGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:271:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:271:                      - - ATCTTGGTCT TCCATATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:272:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:272:                      - - AACAACCTCA ATTTCGAAGA CCAAGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:273:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:273:                      - - ATCTTGGTCT TCGAAATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:274:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:274:                      - - AACAACCTCA ATACCGAAGA CCAAGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:275:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:275:                      - - ATCTTGGTCT TCGGTATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:276:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:276:                      - - AACAACCTCA ATTACGAAGA CCAAGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:277:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:277:                      - - ATCTTGGTCT TCGTAATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:278:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:278:                      - - AACAACCTCA ATGTTGAAGA CCAAGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:279:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:279:                      - - ATCTTGGTCT TCAACATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:280:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:280:                      - - AACAACCTCA ATGGGCGTGA CCAAGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:281:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:281:                      - - ATCTTGGTCT CGCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:282:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:282:                      - - AACAACCTCA ATGGGCAGGA CCAAGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:283:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:283:                      - - ATCTTGGTCC TGCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:284:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:284:                      - - AACAACCTCA ATGGGGGTGA CCAAGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:285:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:285:                      - - ATCTTGGTCA CCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:286:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:286:                      - - AACAACCTCA ATGGGACCGA CCAAGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:287:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:287:                      - - ATCTTGGTCG GTCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:288:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:288:                      - - AACAACCTCA ATGGGGAAGC TCAAGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:289:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:289:                      - - ATCTTGAGCT TCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:290:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:290:                      - - AACAACCTCA ATGGGGAAAA CCAAGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:291:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:291:                      - - ATCTTGGTTT TCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:292:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:292:                      - - AACAACCTCA ATGGGGAACA GCAAGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:293:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:293:                      - - ATCTTGCTGT TCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:294:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:294:                      - - AACAACCTCA ATGGGGAAGA ACAAGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:295:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:295:                      - - ATCTTGTTCT TCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:296:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:296:                      - - AACAACCTCA ATGGGGAAGA CGCTGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:297:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:297:                      - - ATCAGCGTCT TCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:298:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:298:                      - - AACAACCTCA ATGGGGAAGA CCGTGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:299:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:299:                      - - ATCACGGTCT TCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:300:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:300:                      - - AACAACCTCA ATGGGGAAGA CAACGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:301:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:301:                      - - ATCGTTGTCT TCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:302:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:302:                      - - AACAACCTCA ATGGGGAAGA CGACGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:303:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:303:                      - - ATCGTCGTCT TCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:304:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:304:                      - - AACAACCTCA ATGGTGAAGA CGAAGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:305:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:305:                      - - ATCTTCGTCT TCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:306:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:306:                      - - AACAACCTCA ATGGTGAAGA CCACGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:307:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:307:                      - - ATCGTGGTCT TCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:308:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:308:                      - - AACAACCTCA ATGGGGAAGA CATCGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:309:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:309:                      - - ATCGATGTCT TCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:310:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:310:                      - - AACAACCTCA ATGGGGAAGA CTCCGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:311:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:311:                      - - ATCGGAGTCT TCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:312:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:312:                      - - AACAACCTCA ATGGGGAAGA CCAAGCT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:313:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:313:                      - - AGCTTGGTCT TCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:314:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:314:                      - - AACAACCTCA ATGGGGAAGA CCAAAAC          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:315:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:315:                      - - GTTTTGGTCT TCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:316:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:316:                      - - AACAACCTCA ATGGGGAAGA CCAACAG          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:317:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:317:                      - - CTGTTGGTCT TCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:318:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:318:                      - - AACAACCTCA ATGGGGAAGA CCAAGAA          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:319:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:319:                      - - TTCTTGGTCT TCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:320:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:320:                      - - AACAACCTCA ATGGGGAAGA CCAACAC          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:321:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:321:                      - - GTGTTGGTCT TCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:322:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:322:                      - - AACAACCTCA ATGGGGAAGA CCAAATC          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:323:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:323:                      - - GATTTGGTCT TCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:324:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:324:                      - - AACAACCTCA ATGGGGAAGA CCAACTG          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:325:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:325:                      - - CAGTTGGTCT TCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:326:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:326:                      - - AACAACCTCA ATGGGGAAGA CCAAAAA          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:327:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:327:                      - - TTTTTGGTCT TCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:328:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:328:                      - - AACAACCTCA ATGGGGAAGA CCAATAC          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:329:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:329:                      - - GTATTGGTCT TCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:330:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:330:                      - - AACAACCTCA ATGGGGAAGA CCAAGTT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:331:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:331:                      - - AACTTGGTCT TCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:332:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:332:                      - - ATCGCTATGG AAAATAACCT TCGAAGGCCA AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:333:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:333:                      - - CCTTCGAAGG TTATTTTCCA TAGCGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:334:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:334:                      - - ATCGAAATGG AAAATAACCT TCGAAGGCCA AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:335:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:335:                      - - CCTTCGAAGG TTATTTTCCA TTTCGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:336:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:336:                      - - ATCAAAATGG AAAATAACCT TCGAAGGCCA AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:337:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:337:                      - - CCTTCGAAGG TTATTTTCCA TTTTGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:338:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:338:                      - - ATCATGATGG AAAATAACCT TCGAAGGCCA AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:339:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:339:                      - - CCTTCGAAGG TTATTTTCCA TCATGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:340:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:340:                      - - ATCACCATGG AAAATAACCT TCGAAGGCCA AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:341:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:341:                      - - CCTTCGAAGG TTATTTTCCA TGGTGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:342:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:342:                      - - ATCGTTATGG AAAATAACCT TCGAAGGCCA AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:343:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:343:                      - - CCTTCGAAGG TTATTTTCCA TAACGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:344:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:344:                      - - ATCCTGATGC ACAATAACCT TCGAAGGCCA AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:345:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:345:                      - - CCTTCGAAGG TTATTGTGCA TCAGGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:346:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:346:                      - - ATCCTGATGA TGAATAACCT TCGAAGGCCA AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:347:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:347:                      - - CCTTCGAAGG TTATTCATCA TCAGGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:348:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:348:                      - - ATCCTGATGT TCAATAACCT TCGAAGGCCA AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:349:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:349:                      - - CCTTCGAAGG TTATTGAACA TCAGGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:350:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:350:                      - - ATCCTGATGG CTAATAACCT TCGAAGGCCA AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:351:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:351:                      - - CCTTCGAAGG TTATTAGCCA TCAGGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:352:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:352:                      - - ATCCTGATGA ACAATAACCT TCGAAGGCCA AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:353:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:353:                      - - CCTTCGAAGG TTATTGTTCA TCAGGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:354:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:354:                      - - ATCCTGATGA TCAATAACCT TCGAAGGCCA AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:355:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:355:                      - - CCTTCGAAGG TTATTGATCA TCAGGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:356:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:356:                      - - ATCCTGATGA AAAATAACCT TCGAAGGCCA AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:357:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:357:                      - - CCTTCGAAGG TTATTTTTCA TCAGGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:358:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:358:                      - - ATCCTGATGT CCAATAACCT TCGAAGGCCA AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:359:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:359:                      - - CCTTCGAAGG TTATTGGACA TCAGGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:360:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:360:                      - - ATCCTGATGG TTAATAACCT TCGAAGGCCA AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:361:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:361:                      - - CCTTCGAAGG TTATTAACCA TCAGGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:362:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:362:                      - - ATCCTGATGG AAAATAACCT TGCTAGGCCA AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:363:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:363:                      - - CCTAGCAAGG TTATTTTCCA TCAGGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:364:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:364:                      - - ATCCTGATGG AAAATAACCT TAACAGGCCA AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:365:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:365:                      - - CCTGTTAAGG TTATTTTCCA TCAGGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:366:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:366:                      - - ATCCTGATGG AAAATAACCT TCACAGGCCA AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:367:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:367:                      - - CCTGTGAAGG TTATTTTCCA TCAGGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:368:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:368:                      - - ATCCTGATGG AAAATAACCT TAAAAGGCCA AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:369:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:369:                      - - CCTTTTAAGG TTATTTTCCA TCAGGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:370:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:370:                      - - ATCCTGATGG AAAATAACCT TCGAAGGGCT AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:371:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:371:                      - - CCTGTTGAAT GCCTCCAGGT TAGC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:372:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:372:                      - - ATCCTGATGG AAAATAACCT TCGAAGGCGT AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:373:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:373:                      - - CCTGTTGAAT GCCTCCAGGT TACG          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:374:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:374:                      - - ATCCTGATGG AAAATAACCT TCGAAGGAAC AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:375:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:375:                      - - CCTGTTGAAT GCCTCCAGGT TGTT          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:376:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:376:                      - - ATCCTGATGG AAAATAACCT TCGAAGGGAA AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:377:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:377:                      - - CCTGTTGAAT GCCTCCAGGT TTTC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:378:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:378:                      - - ATCCTGATGG AAAATAACCT TCGAAGGCAC AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:379:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:379:                      - - CCTGTTGAAT GCCTCCAGGT TGTG          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:380:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:380:                      - - ATCCTGATGG AAAATAACCT TCGAAGGCTG AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:381:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:381:                      - - CCTGTTGAAT GCCTCCAGGT TCAG          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:382:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:382:                      - - ATCCTGATGG AAAATAACCT TCGAAGGTTC AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:383:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:383:                      - - CCTGTTGAAT GCCTCCAGGT TGAA          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:384:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:384:                      - - ATCCTGATGG AAAATAACCT TCGAAGGACC AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:385:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:385:                      - - CCTGTTGAAT GCCTCCAGGT TGGT          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:386:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:386:                      - - ATCCTGATGG AAAATAACCT TCGAAGGTAC AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:387:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:387:                      - - CCTGTTGAAT GCCTCCAGGT TGTA          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:388:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:388:                      - - ATCCTGATGG AAAATAACCT TCGAAGGGTT AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:389:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:389:                      - - CCTGTTGAAT GCCTCCAGGT TAAC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:390:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:390:                      - - AAAAATCTCG CTCCATGT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:391:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:391:                      - - AGCGAGATTT TTAAGAAT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:392:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:392:                      - - AAAAATCTCA ACCCATGT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:393:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:393:                      - - GTTGAGATTT TTAAGAAT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:394:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:394:                      - - AAAAATCTCG AACCATGT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:395:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:395:                      - - TTCGAGATTT TTAAGAAT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:396:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:396:                      - - AAAAATCTCC ACCCATGT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:397:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:397:                      - - GTGGAGATTT TTAAGAAT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:398:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:398:                      - - AAAAATCTCA TCCCATGT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:399:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:399:                      - - GATGAGATTT TTAAGAAT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:400:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:400:                      - - AAAAATCTCA TGCCATGT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:401:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:401:                      - - CATGAGATTT TTAAGAAT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:402:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:402:                      - - AAAAATCTCT TCCCATGT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:403:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:403:                      - - GAAGAGATTT TTAAGAAT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:404:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:404:                      - - AAAAATCTCT CCCCATGT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:405:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:405:                      - - GGAGAGATTT TTAAGAAT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:406:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:406:                      - - AAAAATCTCA CCCCATGT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:407:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:407:                      - - GGTGAGATTT TTAAGAAT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:408:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:408:                      - - AAAAATCTCT ACCCATGT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:409:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:409:                      - - GTAGAGATTT TTAAGAAT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:410:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:410:                      - - CTGCCCCTGG CCACGGCCGC AGCTACG          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:411:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:411:                      - - ATGGATTGGA TGTCGCGTAG CTGC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:412:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:412:                      - - CTGCCCCTGG CCACGGCCGC AGGTACG          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:413:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:413:                      - - ATGGATTGGA TGTCGCGTAC CTGC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:414:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:414:                      - - CTGCCCCTGG CCACGGCCGC AATCACG          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:415:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:415:                      - - ATGGATTGGA TGTCGCGTGA TTGC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:416:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 21 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:416:                      - - GCTCATCCAA TCCATATCAA G           - #                  - #                      - #21                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:417:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:417:                      - - ATGGATTGGA TGAGCCGTGG GTGC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:418:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 21 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:418:                      - - CAGCATCCAA TCCATATCAA G           - #                  - #                      - #21                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:419:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:419:                      - - ATGGATTGGA TGCTGCGTGG GTGC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:420:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 21 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:420:                      - - CACCATCCAA TCCATATCAA G           - #                  - #                      - #21                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:421:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:421:                      - - ATGGATTGGA TGGTGCGTGG GTGC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:422:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 21 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:422:                      - - AAACATCCAA TCCATATCAA G           - #                  - #                      - #21                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:423:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:423:                      - - ATGGATTGGA TGTTTCGTGG GTGC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:424:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 21 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:424:                      - - CGAGCTCCAA TCCATATCAA G           - #                  - #                      - #21                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:425:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:425:                      - - ATGGATTGGA GCTCGCGTGG GTGC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:426:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 21 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:426:                      - - CGAAACCCAA TCCATATCAA G           - #                  - #                      - #21                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:427:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:427:                      - - ATGGATTGGG TTTCGCGTGG GTGC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:428:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 21 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:428:                      - - CGAGACCCAA TCCATATCAA G           - #                  - #                      - #21                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:429:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:429:                      - - ATGGATTGGG TCTCGCGTGG GTGC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:430:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 21 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:430:                      - - CGAATCCCAA TCCATATCAA G           - #                  - #                      - #21                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:431:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:431:                      - - ATGGATTGGG ATTCGCGTGG GTGC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:432:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 21 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:432:                      - - CGAAAACCAA TCCATATCAA G           - #                  - #                      - #21                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:433:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:433:                      - - ATGGATTGGT TTTCGCGTGG GTGC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:434:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 21 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:434:                      - - CGAATGCCAA TCCATATCAA G           - #                  - #                      - #21                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:435:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:435:                      - - ATGGATTGGC ATTCGCGTGG GTGC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:436:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 21 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:436:                      - - CGATTCCCAA TCCATATCAA G           - #                  - #                      - #21                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:437:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:437:                      - - ATGGATTGGG AATCGCGTGG GTGC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:438:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 21 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:438:                      - - CGATCCCCAA TCCATATCAA G           - #                  - #                      - #21                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:439:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:439:                      - - ATGGATTGGG GATCGCGTGG GTGC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:440:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 21 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:440:                      - - CGATGGCCAA TCCATATCAA G           - #                  - #                      - #21                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:441:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:441:                      - - ATGGATTGGC CATCGCGTGG GTGC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:442:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 21 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:442:                      - - CGATACCCAA TCCATATCAA G           - #                  - #                      - #21                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:443:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:443:                      - - ATGGATTGGG TATCGCGTGG GTGC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:444:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 34 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:444:                      - - CATCCAATCC AAATCAAGGA CGGTGACTGG AATG       - #                  -      #        34                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:445:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 44 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:445:                      - - AATTCATTCC AGTCACCGTC CTTGATTTGG ATTGGATGTC GCGT   - #                      - # 44                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:446:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 34 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:446:                      - - CATCCAATCG AAATCAAGGA CGGTGACTGG AATG       - #                  -      #        34                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:447:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 44 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:447:                      - - AATTCATTCC AGTCACCGTC CTTGATTTCG ATTGGATGTC GCGT   - #                      - # 44                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:448:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 34 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:448:                      - - CATCCAATCA TGATCAAGGA CGGTGACTGG AATG       - #                  -      #        34                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:449:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 44 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:449:                      - - AATTCATTCC AGTCACCGTC CTTGATCATG ATTGGATGTC GCGT   - #                      - # 44                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:450:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 34 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:450:                      - - CATCCAATCT TCATCAAGGA CGGTGACTGG AATG       - #                  -      #        34                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:451:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 44 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:451:                      - - AATTCATTCC AGTCACCGTC CTTGATGAAG ATTGGATGTC GCGT   - #                      - # 44                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:452:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 34 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:452:                      - - CATCCAATCT CCATCAAGGA CGGTGACTGG AATG       - #                  -      #        34                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:453:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 44 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:453:                      - - AATTCATTCC AGTCACCGTC CTTGATGGAG ATTGGATGTC GCGT   - #                      - # 44                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:454:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 34 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:454:                      - - CATCCAATCG TAATCAAGGA CGGTGACTGG AATG       - #                  -      #        34                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:455:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 44 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:455:                      - - AATTCATTCC AGTCACCGTC CTTGATTACG ATTGGATGTC GCGT   - #                      - # 44                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:456:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 21 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:456:                      - - CGACATCCAA TCCGTATCAA G           - #                  - #                      - #21                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:457:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:457:                      - - ACGGATTGGA TGTCGCGTGG GTGC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:458:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 21 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:458:                      - - CGACATCCAA TCAAAATCAA G           - #                  - #                      - #21                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:459:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:459:                      - - TTTGATTGGA TGTCGCGTGG GTGC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:460:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 21 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:460:                      - - CGACATCCAA TCTACATCAA G           - #                  - #                      - #21                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:461:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:461:                      - - GTAGATTGGA TGTCGCGTGG GTGC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:462:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 16 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:462:                      - - GCTGGTGACT GGAATG             - #                  - #                      - #    16                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:463:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 26 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:463:                      - - AATTCATTCC AGTCACCAGC CTTGAT          - #                  - #                  26                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:464:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 16 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:464:                      - - AACGGTGACT GGAATG             - #                  - #                      - #    16                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:465:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 26 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:465:                      - - AATTCATTCC AGTCACCGTT CTTGAT          - #                  - #                  26                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:466:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 16 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:466:                      - - GAAGGTGACT GGAATG             - #                  - #                      - #    16                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:467:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 26 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:467:                      - - AATTCATTCC AGTCACCTTC CTTGAT          - #                  - #                  26                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:468:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 16 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:468:                      - - GGTGGTGACT GGAATG             - #                  - #                      - #    16                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:469:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 26 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:469:                      - - AATTCATTCC AGTCACCACC CTTGAT          - #                  - #                  26                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:470:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 16 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:470:                      - - ATCGGTGACT GGAATG             - #                  - #                      - #    16                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:471:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 26 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:471:                      - - AATTCATTCC AGTCACCGAT CTTGAT          - #                  - #                  26                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:472:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 16 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:472:                      - - CTGGGTGACT GGAATG             - #                  - #                      - #    16                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:473:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 26 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:473:                      - - AATTCATTCC AGTCACCCAG CTTGAT          - #                  - #                  26                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:474:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 16 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:474:                      - - TTCGGTGACT GGAATG             - #                  - #                      - #    16                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:475:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 26 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:475:                      - - AATTCATTCC AGTCACCGAA CTTGAT          - #                  - #                  26                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:476:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 16 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:476:                      - - TCCGGTGACT GGAATG             - #                  - #                      - #    16                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:477:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 26 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:477:                      - - AATTCATTCC AGTCACCGGA CTTGAT          - #                  - #                  26                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:478:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:478:                      - - AATTCGCTAG GAAACTGACG TTCTATCTGA AA       - #                  - #              32                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:479:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:479:                      - - CTCAAGGGTT TTCAGATAGA ACGTCAGTTT CCTAGCG      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:480:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:480:                      - - AATTCCAGAG GAAACTGACG TTCTATCTGA AA       - #                  - #              32                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:481:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:481:                      - - CTCAAGGGTT TTCAGATAGA ACGTCAGTTT CCTCTGG      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:482:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:482:                      - - AATTCCACAG GAAACTGACG TTCTATCTGA AA       - #                  - #              32                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:483:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:483:                      - - CTCAAGGGTT TTCAGATAGA ACGTCAGTTT CCTGTGG      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:484:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:484:                      - - AATTCTCCAG GAAACTGACG TTCTATCTGA AA       - #                  - #              32                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:485:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:485:                      - - CTCAAGGGTT TTCAGATAGA ACGTCAGTTT CCTGGAG      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:486:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:486:                      - - AATTCCGGAG GCGTCTGACG TTCTATCTGA AA       - #                  - #              32                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:487:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:487:                      - - CTCAAGGGTT TTCAGATAGA ACGTCAGACG CCTCCGG      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:488:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:488:                      - - AATTCCGGAG GGAACTGACG TTCTATCTGA AA       - #                  - #              32                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:489:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:489:                      - - CTCAAGGGTT TTCAGATAGA ACGTCAGTTC CCTCCGG      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:490:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:490:                      - - AATTCCGGAG GCACCTGACG TTCTATCTGA AA       - #                  - #              32                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:491:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:491:                      - - CTCAAGGGTT TTCAGATAGA ACGTCAGGTG CCTCCGG      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:492:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:492:                      - - AATTCCGGAG GATCCTGACG TTCTATCTGA AA       - #                  - #              32                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:493:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:493:                      - - CTCAAGGGTT TTCAGATAGA ACGTCAGGAT CCTCCGG      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:494:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:494:                      - - AATTCCGGAG GTCCCTGACG TTCTATCTGA AA       - #                  - #              32                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:495:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:495:                      - - CTCAAGGGTT TTCAGATAGA ACGTCAGGGA CCTCCGG      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:496:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:496:                      - - AATTCCGGAG GAAACTGACG GACTATCTGA AA       - #                  - #              32                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:497:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:497:                      - - CTCAAGGGTT TTCAGATAGT CCGTCAGTTT CCTCCGG      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:498:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:498:                      - - AATTCCGGAG GAAACTGACG ATCTATCTGA AA       - #                  - #              32                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:499:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:499:                      - - CTCAAGGGTT TTCAGATAGA TCGTCAGTTT CCTCCGG      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:500:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:500:                      - - AATTCCGGAG GAAACTGACG CTGTATCTGA AA       - #                  - #              32                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:501:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:501:                      - - CTCAAGGGTT TTCAGATACA GCGTCAGTTT CCTCCGG      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:502:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:502:                      - - AATTCCGGAG GAAACTGACG AAATATCTGA AA       - #                  - #              32                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:503:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:503:                      - - CTCAAGGGTT TTCAGATATT TCGTCAGTTT CCTCCGG      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:504:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:504:                      - - AATTCCGGAG GAAACTGACG GTTTATCTGA AA       - #                  - #              32                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:505:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:505:                      - - CTCAAGGGTT TTCAGATAAA CCGTCAGTTT CCTCCGG      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:506:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:506:                      - - AATTCCGGAG GAAACTGACG TTCTATCTGG CT       - #                  - #              32                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:507:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:507:                      - - CTCAAGGGTA GCCAGATAGA ACGTCAGTTT CCTCCGG      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:508:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:508:                      - - AATTCCGGAG GAAACTGACG TTCTATCTGC GT       - #                  - #              32                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:509:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:509:                      - - CTCAAGGGTA CGCAGATAGA ACGTCAGTTT CCTCCGG      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:510:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:510:                      - - AATTCCGGAG GAAACTGACG TTCTATCTGA AC       - #                  - #              32                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:511:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:511:                      - - CTCAAGGGTG TTCAGATAGA ACGTCAGTTT CCTCCGG      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:512:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:512:                      - - AATTCCGGAG GAAACTGACG TTCTATCTGC AG       - #                  - #              32                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:513:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:513:                      - - CTCAAGGGTC TGCAGATAGA ACGTCAGTTT CCTCCGG      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:514:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:514:                      - - AATTCCGGAG GAAACTGACG TTCTATCTGC AC       - #                  - #              32                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:515:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:515:                      - - CTCAAGGGTG TGCAGATAGA ACGTCAGTTT CCTCCGG      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:516:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:516:                      - - AATTCCGGAG GAAACTGACG TTCTATCTGA TG       - #                  - #              32                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:517:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:517:                      - - CTCAAGGGTC ATCAGATAGA ACGTCAGTTT CCTCCGG      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:518:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:518:                      - - AATTCCGGAG GAAACTGACG TTCTATCTGT TC       - #                  - #              32                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:519:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:519:                      - - CTCAAGGGTG AACAGATAGA ACGTCAGTTT CCTCCGG      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:520:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:520:                      - - AATTCCGGAG GAAACTGACG TTCTATCTGT AC       - #                  - #              32                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:521:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:521:                      - - CTCAAGGGTG TACAGATAGA ACGTCAGTTT CCTCCGG      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:522:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 40 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:522:                      - - CATGGCTAAC TGCTCTAACA TGATCGATGA AATTATAACA     - #                      - #    40                                                                     - -  - - (2) INFORMATION FOR SEQ ID NO:523:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:523:                      - - CACTTAAAGC AGCCACCTTT GCCTTTGCTG GACTTC      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:524:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:524:                      - - AACAACCTCA ATGGGGAAGA CCAAGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:525:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 45 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:525:                      - - CTTTAAGTGT GTTATAATTT CATCGATCAT GTTAGAGCAG TTAGC   - #                      - #45                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:526:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:526:                      - - GAGGTTGTTG AAGTCCAGCA AAGGCAAAGG TGGCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:527:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:527:                      - - ATCTTGGTCT TCCCCATT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:528:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 36 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:528:                      - - ATCCTGATGG AAAATAACCT TCGAAGGCCA AACCTG      - #                  -     #       36                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:529:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:529:                      - - GAGGCATTCA ACAGGGCTGT CAAG          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:530:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 15 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:530:                      - - AGTTTACAGA ATGCA              - #                  - #                      - #    15                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:531:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:531:                      - - CCTTCGAAGG TTATTTTCCA TCAGGAT          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:532:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:532:                      - - CCTGTTGAAT GCCTCCAGGT TTGG          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:533:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 20 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:533:                      - - TTCTGTAAAC TCTTGACAGC            - #                  - #                      - # 20                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:534:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 21 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:534:                      - - TCAGCAATTG AGAGCATTCT T           - #                  - #                      - #21                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:535:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:535:                      - - AAAAATCTCC TGCCATGT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:536:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 48 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:536:                      - - CTGCCCCTGG CCACGGCCGC ACCCACGCGA CATCCAATCC ATATCAAG  - #                    48                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:537:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:537:                      - - CTGCCCCTGG CCACGGCCGC ACCCACG          - #                  - #                 27                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:538:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 21 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:538:                      - - CGACATCCAA TCCATATCAA G           - #                  - #                      - #21                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:539:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 16 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:539:                      - - GACGGTGACT GGAATG             - #                  - #                      - #    16                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:540:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 19 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:540:                      - - GCTCTCAATT GCTGATGCA             - #                  - #                      - # 19                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:541:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 18 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:541:                      - - CAGGAGATTT TTAAGAAT             - #                  - #                      - #  18                                                                   - -  - - (2) INFORMATION FOR SEQ ID NO:542:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 48 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:542:                      - - ATGGATTGGA TGTCGCGTGG GTGCGGCCGT GGCCAGGGGC AGACATGG  - #                    48                                                                         - -  - - (2) INFORMATION FOR SEQ ID NO:543:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:543:                      - - GGCCGTGGCC AGGGGCAGAC ATGG          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:544:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 24 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:544:                      - - ATGGATTGGA TGTCGCGTGG GTGC          - #                  - #                    24                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:545:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 26 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:545:                      - - AATTCATTCC AGTCACCGTC CTTGAT          - #                  - #                  26                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:546:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:546:                      - - AATTCCGGAG GAAACTGACG TTCTATCTGA AA       - #                  - #              32                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:547:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 32 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:547:                      - - ACCCTTGAGA ATGCGCAGGC TCAACAGTAA TA       - #                  - #              32                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:548:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 37 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:548:                      - - CTCAAGGGTT TTCAGATAGA ACGTCAGTTT CCTCCGG      - #                       - #      37                                                                      - -  - - (2) INFORMATION FOR SEQ ID NO:549:                                   - -      (i) SEQUENCE CHARACTERISTICS:                                                 (A) LENGTH: 27 base - #pairs                                                  (B) TYPE: nucleic acid                                                        (C) STRANDEDNESS: single                                                      (D) TOPOLOGY: linear                                                 - -     (ii) MOLECULE TYPE: DNA (synthetic)                                   - -         (xi) SEQUENCE DESCRIPTION: SEQ - #ID NO:549:                      - - AGCTTATTAC TGTTGAGCCT GCGCATT          - #                  - #                 27                                                                     - - 2/219                                                                   __________________________________________________________________________

What is claimed is:
 1. A method of treating a patient having animmunodeficiency or hematopoietic disorder comprising administering tosaid patient, a therapeutically effective amount of a mutant humaninterleukin-3 (hIL-3) polypeptide comprising a modified hIL-3 amino acidsequence selected from the group consisting of:(a) a sequence of (SEQ IDNO:15)wherein; Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, orArg; Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln; Xaa atposition 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys; Xaa at position 20is Ile, Cys, Gln, Glu, Arg, Pro, or Ala; Xaa at position 21 is Asp, Phe,Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val; Xaa at position 22is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly; Xaa atposition 23 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg; Xaaat position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu; Xaa at position25 is Thr, His, Gly, Gln, Arg, Pro, or Ala; Xaa at position 26 is His,Thr, Phe, Gly, Arg, Ala, or Trp; Xaa at position 27 is Leu, Gly, Arg,Thr, Ser, or Ala; Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro,Val or Trp; Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val; Xaaat position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys; Xaa atposition 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa at position 32is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 33 is Pro,Leu, Gln, Ala, Thr, or Glu; Xaa at position 34 is Leu, Val, Gly, Ser,Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaa at position 35 isLeu, Ala, Gly, Asn, Pro, Gln, or Val; Xaa at position 36 is Asp, Leu, orVal; Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile; Xaa at position38 is Asn, or Ala; Xaa at position 40 is Leu, Trp, or Arg; Xaa atposition 41 is Asn, Cys, Arg, Leu, His, Met, or Pro; Xaa at position 42is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Metor Ala; Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys,Gln, Arg, Thr, Gly or Ser; Xaa at position 44 is Asp, Ser, Leu, Arg,Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro; Xaa at position 45 isGln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala,Ile, Glu or His; Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu,Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaa at position 47 isIle, Gly, Val, Ser, Arg, Pro, or His; Xaa at position 48 is Leu, Ser,Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn; Xaa atposition 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa atposition 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val,His, Phe, Met or Gln; Xaa at position 51 is Asn, Arg, Met, Pro, Ser,Thr, or His; Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His,Ala or Leu; Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly; Xaaat position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr,Phe, Leu, Val or Lys; Xaa at position 57 is Asn or Gly; Xaa at position58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys; Xaa at position 59 is Glu,Tyr, His, Leu, Pro, or Arg; Xaa at position 60 is Ala, Ser, Pro, Tyr,Asn, or Thr; Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile; Xaa atposition 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val; Xaa atposition 64 is Ala, Asn, Pro, Ser, or Lys; Xaa at position 65 is Val,Thr, Pro, His, Leu, Phe, or Ser; Xaa at position 66 is Lys, Ile, Arg,Val, Asn, Glu, or Ser; Xaa at position 67 is Ser, Ala, Phe, Val, Gly,Asn, Ile, Pro, or His; Xaa at position 68 is Leu, Val, Trp, Ser, Ile,Phe, Thr, or His; Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg,Trp, Gly, or Leu; Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, orAsn; Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa atposition 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala; Xaa at position 75 isGlu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu; Xaa at position 76is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp; Xaa at position 77 isIle, Ser, Arg, Thr, or Leu; Xaa at position 78 is Leu, Ala, Ser, Glu,Phe, Gly, or Arg; Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile,Gly, or Asp; Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, orArg; Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr,Ser, Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 83 is Pro, Ala,Thr, Trp, Arg, or Met; Xaa at position 84 is Cys, Glu, Gly, Arg, Met, orVal; Xaa at position 85 is Leu, Asn, Val, or Gln; Xaa at position 86 isPro, Cys, Arg, Ala, or Lys; Xaa at position 87 is Leu, Ser, Trp, or Gly;Xaa at position 88 is Ala, Lys, Arg, Val, or Trp; Xaa at position 89 isThr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 90 isAla, Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 91 is Ala,Pro, Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 92 is Pro, Phe,Arg, Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 93 is Thr,Asp, Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 94 is Arg, Ile,Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro; Xaa at position 95 isHis, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe,Ile, or Tyr; Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaaat position 97 is Ile, Val, Lys, Ala, or Asn; Xaa at position 98 is His,Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg,Tyr or Pro; Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln,Gly, Ser, Phe, or His; Xaa at position 100 is Lys, Tyr, Leu, His, Arg,Ile, Ser, Gln, or Pro; Xaa at position 101 is Asp; Xaa at position 102is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 103 is Asp, orSer; Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln,Lys, Ala, Phe, or Gly; Xaa at position 105 is Asn, Pro, Ala, Phe, Ser,Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 106 is Glu,Ser, Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 108 is Arg, Lys,Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro; Xaa at position 109 isArg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 110 is Lys,Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, Ala, or Trp; Xaa atposition 111 is Leu, Ile, Arg, Asp, or Met; Xaa at position 112 is Thr,Val, Gln, Tyr, Glu, His, Ser, or Phe; Xaa at position 113 is Phe, Ser,Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 115 is Leu,Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 116 isLys; Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa atposition 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa atposition 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa atposition 120 is Asn, Ala, Pro, Leu, His, Val, or Gln; Xaa at position121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly; Xaa at position 122 isGln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa atposition 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;wherein fromone to three of the amino acids designated by Xaa are different from thecorresponding amino acids of native (1-133) human interleukin-3; andwherein from 1 to 14 amino acids are optionally deleted from theN-terminus and/or from 1 to 15 amino acids are optionally deleted fromthe C-terminus; and said mutant human interleukin-3 polypeptide has atleast three times greater cell proliferative activity than native humaninterleukin-3 in at least one assay selected from the group consistingof: AML cell proliferation, TF-1 cell proliferation and Methylcelluloseassay; and (b) a polypeptide comprising an N-terminal methionineresidue, alanine residue or methionine-alanine di-peptide immediatelypreceding said sequence according to (a).
 2. The method according toclaim 1, wherein said mutant human interleukin-3 polypeptide has atleast ten times greater cell proliferative activity than native humaninterleukin-3.
 3. The method according to claim 1 wherein in said mutanthuman interleukin-3 (hIL-3) sequence the amino acids which differ fromthe corresponding residue in native human interleukin-3 are selectedfrom the group consisting of:position 42 wherein Xaa is Gly, Asp, Ser,Ile, Leu, Met, Tyr, or Ala; position 45 wherein Xaa is Gln, Val, Met orAsn; position 46 wherein Xaa is Asp, Ser, Gln, His or Val; position 50wherein Xaa is Glu or Asp; position 51 wherein Xaa is Asn, Pro or Thr;position 62 wherein Xaa is Asn or Pro; position 76 wherein Xaa is Ser,or Pro; position 82 wherein Xaa is Leu, Trp, Asp, Asn Glu, His, Phe, Seror Tyr; position 95 wherein Xaa is His, Arg, Thr, Asn or Ser; position98 wherein Xaa is His, Ile, Leu, Ala, Gln, Lys, Met, Ser, Tyr or Val;position 100 wherein Xaa is Lys or Arg; position 101 wherein Xaa is Asp;position 105 wherein Xaa is Asn, or Pro; position 108 wherein Xaa isArg, Ala, or Ser; position 116 wherein Xaa is Lys; position 121 whereinXaa is Ala, or Ile; position 122 wherein Xaa is Gln, or Ile; position123 wherein Xaa is Ala, Met or Glu.
 4. The method according to claim 3,wherein said mutant human interleukin-3 polypeptide has at least tentimes greater cell proliferative activity than native humaninterleukin-3.
 5. A method of treating a patient having animmunodeficiency or hematopoietic disorder comprising administering tosaid patient, a therapeutically effective amount of a mutant humaninterleukin-3 (hIL-3) polypeptide comprising a modified hIL-3 amino acidsequence selected from the group consisting of:(a) a sequence of (SEQ IDNO:17)wherein; Xaa at position 17 is Ser, Gly, Asp, Met, or Gln; Xaa atposition 18 is Asn, His, or Ile; Xaa at position 19 is Met or Ile; Xaaat position 21 is Asp or Glu; Xaa at position 23 is Ile, Ala, Leu, orGly; Xaa at position 24 is Ile, Val, or Leu; Xaa at position 25 is Thr,His, Gln, or Ala; Xaa at position 26 is His or Ala; Xaa at position 29is Gln, Asn, or Val; Xaa at position 30 is Pro, Gly, or Gln; Xaa atposition 31 is Pro, Asp, Gly, or Gln; Xaa at position 32 is Leu, Arg,Gln, Asn, Gly, Ala, or Glu; Xaa at position 33 is Pro or Glu; Xaa atposition 34 is Leu, Val, Gly, Ser, Lys, Ala, Arg, Gln, Glu, Ile, Phe,Thr or Met; Xaa at position 35 is Leu, Ala, Asn, Pro, Gln, or Val; Xaaat position 37 is Phe, Ser, Pro, or Trp; Xaa at position 38 is Asn orAla; Xaa at position 42 is Gly, Asp, Ser, Cys, Ala, Asn, Ile, Leu, Met,Tyr or Arg; Xaa at position 44 is Asp or Glu; Xaa at position 45 is Gln,Val, Met, Leu, Thr, Ala, Asn, Glu, Ser or Lys; Xaa at position 46 isAsp, Phe, Ser, Thr, Ala, Asn, Gln, Glu, His, Ile, Lys, Tyr, Val or Cys;Xaa at position 50 is Glu, Ala, Asn, Ser or Asp; Xaa at position 51 isAsn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 54 is Arg or Ala;Xaa at position 55 is Arg, Thr, Val, Leu, or Gly; Xaa at position 56 isPro, Gly, Ser, Gln, Ala, Arg, Asn, Glu, Leu, Thr, Val or Lys; Xaa atposition 60 is Ala or Ser; Xaa at position 62 is Asn, Pro, Thr, or Ile;Xaa at position 63 is Arg or Lys; Xaa at position 64 is Ala or Asn; Xaaat position 65 is Val or Thr; Xaa at position 66 is Lys or Arg; Xaa atposition 67 is Ser, Phe, or His; Xaa at position 68 is Leu, Ile, Phe, orHis; Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, or Gly; Xaa atposition 71 is Ala, Pro, or Arg; Xaa at position 72 is Ser, Glu, Arg, orAsp; Xaa at position 73 is Ala or Leu; Xaa at position 76 is Ser, Val,Ala, Asn, Glu, Pro, or Gly; Xaa at position 77 is Ile or Leu; Xaa atposition 79 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp; Xaa atposition 80 is Asn, Gly, Glu, or Arg; Xaa at position 82 is Leu, Gln,Trp, Arg, Asp, Ala, Asn, Glu, His, Ile, Met, Phe, Ser, Thr, Tyr or Val;Xaa at position 83 is Pro or Thr; Xaa at position 85 is Leu or Val; Xaaat position 87 is Leu or Ser; Xaa at position 88 is Ala or Trp; Xaa atposition 91 is Ala or Pro; Xaa at position 93 is Thr, Asp, Ser, Pro,Ala, Leu, or Arg; Xaa at position 95 is His, Pro, Arg, Val, Leu, Gly,Asn, Phe, Ser or Thr; Xaa at position 96 is Pro or Tyr; Xaa at position97 is Ile or Val; Xaa at position 98 is His, Ile, Asn, Leu, Ala, Thr,Arg, Gln, Lys, Met, Ser, Tyr, Val or Pro; Xaa at position 99 is Ile,Leu, or Val; Xaa at position 100 is Lys, Arg, Ile, Gln, Pro, or Ser; Xaaat position 101 is Asp; Xaa at position 104 is Trp or Leu; Xaa atposition 105 is Asn, Pro, Ala, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp,or His; Xaa at position 106 is Glu or Gly; Xaa at position 108 is Arg,Ala, or Ser; Xaa at position 109 is Arg, Thr, Glu, Leu, or Ser; Xaa atposition 112 is Thr, Val, or Gln; Xaa at position 114 is Tyr or Trp; Xaaat position 115 is Leu or Ala; Xaa at position 116 is Lys; Xaa atposition 117 is Thr or Ser; Xaa at position 120 is Asn, Pro, Leu, His,Val, or Gln; Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Asp, orGly; Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile,Tyr, or Cys; Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr,or Leu;wherein from one to three of the amino acids designated by Xaaare different from the corresponding amino acids of native (1-133) humaninterleukin-3; and wherein from 1 to 14 amino acids are optionallydeleted from the N-terminus and/or from 1 to 15 amino acids areoptionally deleted from the C-terminus; and said mutant humaninterleukin-3 polypeptide has at least three times greater cellproliferative activity than native human interleukin-3 in at least oneassay selected from the group consisting of: AML cell proliferation,TF-1 cell proliferation and Methylcellulose assay; and (b) a polypeptidecomprising an N-terminal methionine residue, alanine residue ormethionine-alanine di-peptide immediately preceding said sequenceaccording to (a).
 6. The method according to claim 5, wherein saidmutant human interleukin-3 polypeptide has at least ten times greatercell proliferative activity than native human interleukin-3.
 7. A methodof treating a patient having an immunodeficiency or hematopoieticdisorder comprising administering to said patient, a therapeuticallyeffective amount of a mutant human interleukin-3 (hIL-3) polypeptidecomprising a modified hIL-3 amino acid sequence selected from the groupconsisting of:(a) a sequence of (SEQ ID NO:19)wherein; Xaa at position 3is Ser, Lys, Gly, Asp, Met, Gln, or Arg; Xaa at position 4 is Asn, His,Leu, Ile, Phe, Arg, or Gln; Xaa at position 5 is Met, Phe, Ile, Arg,Gly, Ala, or Cys; Xaa at position 6 is Ile, Cys, Gln, Glu, Arg, Pro, orAla; Xaa at position 7 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn,Thr, Ser or Val; Xaa at position 8 is Glu, Trp, Pro, Ser, Ala, His, Asp,Asn, Gln, Leu, Val, or Gly; Xaa at position 9 is Ile, Val, Ala, Leu,Gly, Trp, Lys, Phe, Ser, or Arg; Xaa at position 10 is Ile, Gly, Val,Arg, Ser, Phe, or Leu; Xaa at position 11 is Thr, His, Gly, Gln, Arg,Pro, or Ala; Xaa at position 12 is His, Thr, Phe, Gly, Arg, Ala, or Trp;Xaa at position 13 is Leu, Gly, Arg, Thr, Ser, or Ala; Xaa at position14 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp; Xaa at position 15 isGln, Asn, Leu, Pro, Arg, or Val; Xaa at position 16 is Pro, His, Thr,Gly, Asp, Gln, Ser, Leu, or Lys; Xaa at position 17 is Pro, Asp, Gly,Ala, Arg, Leu, or Gln; Xaa at position 18 is Leu, Val, Arg, Gln, Asn,Gly, Ala, or Glu; Xaa at position 19 is Pro, Leu, Gln, Ala, Thr, or Glu;Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala,Phe, Ile or Met; Xaa at position 21 is Leu, Ala, Gly, Asn, Pro, Gln, orVal; Xaa at position 22 is Asp, Leu, or Val; Xaa at position 23 is Phe,Ser, Pro, Trp, or Ile; Xaa at position 24 is Asn, or Ala; Xaa atposition 26 is Leu, Trp, or Arg; Xaa at position 27 is Asn, Cys, Arg,Leu, His, Met, Pro; Xaa at position 28 is Gly, Asp, Ser, Cys, Ala, Lys,Asn, Thr, Leu, Val, Glu, Phe, Tyr, Ile or Met; Xaa at position 29 isGlu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser; Xaaat position 30 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln,Ala or Pro; Xaa at position 31 is Gln, Pro, Phe, Val, Met, Leu, Thr,Lys, Asp, Asn, Arg, Ser, Ala, Ile, Glu, His or Trp; Xaa at position 32is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Valor Gly; Xaa at position 33 is Ile, Gly, Val, Ser, Arg, Pro, or His; Xaaat position 34 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala,Met, Val or Asn; Xaa at position 35 is Met, Arg, Ala, Gly, Pro, Asn,His, or Asp; Xaa at position 36 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn,Ser, Ala, Ile, Val, His, Phe, Met or Gln; Xaa at position 37 is Asn,Arg, Met, Pro, Ser, Thr, or His; Xaa at position 38 is Asn, His, Arg,Leu, Gly, Ser, or Thr; Xaa at position 39 is Leu, Thr, Ala, Gly, Glu,Pro, Lys, Ser, or Met; Xaa at position 40 is Arg, Asp, Ile, Ser, Val,Thr, Gln, Asn, Lys, His, Ala or Leu; Xaa at position 41 is Arg, Thr,Val, Ser, Leu, or Gly; Xaa at position 42 is Pro, Gly, Cys, Ser, Gln,Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys; Xaa at position 43is Asn or Gly; Xaa at position 44 is Leu, Ser, Asp, Arg, Gln, Val, orCys; Xaa at position 45 is Glu, Tyr, His, Leu, Pro, or Arg; Xaa atposition 46 is Ala, Ser, Pro, Tyr, Asn, or Thr; Xaa at position 47 isPhe, Asn, Glu, Pro, Lys, Arg, or Ser; Xaa at position 48 is Asn, His,Val, Arg, Pro, Thr, Asp, or Ile; Xaa at position 49 is Arg, Tyr, Trp,Lys, Ser, His, Pro, or Val; Xaa at position 50 is Ala, Asn, Pro, Ser, orLys; Xaa at position 51 is Val, Thr, Pro, His, Leu, Phe, or Ser; Xaa atposition 52 is Lys, Ile, Arg, Val, Asn, Glu, or Ser; Xaa at position 53is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His; Xaa at position 54 isLeu, Val, Trp, Ser, Ile, Phe, Thr, or His; Xaa at position 55 is Gln,Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu; Xaa at position 56 is Asn,Leu, Val, Trp, Pro, or Ala; Xaa at position 57 is Ala, Met, Leu, Pro,Arg, Glu, Thr, Gln, Trp, or Asn; Xaa at position 58 is Ser, Glu, Met,Ala, His, Asn, Arg, or Asp; Xaa at position 59 is Ala, Glu, Asp, Leu,Ser, Gly, Thr, or Arg; Xaa at position 60 is Ile, Met, Thr, Pro, Arg,Gly, Ala; Xaa at position 61 is Glu, Lys, Gly, Asp, Pro, Trp, Arg, Ser,Gln, or Leu; Xaa at position 62 is Ser, Val, Ala, Asn, Trp, Glu, Pro,Gly, or Asp; Xaa at position 63 is Ile, Ser, Arg, Thr, or Leu; Xaa atposition 64 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg; Xaa at position 65is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp; Xaa at position 66 is Asn,Trp, Val, Gly, Thr, Leu, Glu, or Arg; Xaa at position 67 is Leu, Gln,Gly, Ala, Trp, Arg, Val, or Lys; Xaa at position 68 is Leu, Gln, Lys,Trp, Arg, Asp, Glu, Asn, His, Thr, Ser, Ala, Tyr, Phe, Ile, Met or Val;Xaa at position 69 is Pro, Ala, Thr, Trp, Arg, or Met; Xaa at position70 is Cys, Glu, Gly, Arg, Met, or Val; Xaa at position 71 is Leu, Asn,Val, or Gln; Xaa at position 72 is Pro, Cys, Arg, Ala, or Lys; Xaa atposition 73 is Leu, Ser, Trp, or Gly; Xaa at position 74 is Ala, Lys,Arg, Val, or Trp; Xaa at position 75 is Thr, Asp, Cys, Leu, Val, Glu,His, Asn, or Ser; Xaa at position 76 is Ala, Pro, Ser, Thr, Gly, Asp,Ile, or Met; Xaa at position 77 is Ala, Pro, Ser, Thr, Phe, Leu, Asp, orHis; Xaa at position 78 is Pro, Phe, Arg, Ser, Lys, His, Ala, Gly, Ileor Leu; Xaa at position 79 is Thr, Asp, Ser, Asn, Pro, Ala, Leu, or Arg;Xaa at position 80 is Arg, Ile, Ser, Glu, Leu, Val, Gln, Lys, His, Alaor Pro; Xaa at position 81 is His, Gln, Pro, Arg, Val, Leu, Gly, Thr,Asn, Lys, Ser, Ala, Trp, Phe, Ile or Tyr; Xaa at position 82 is Pro,Lys, Tyr, Gly, Ile, or Thr; Xaa at position 83 is Ile, Val, Lys, Ala, orAsn; Xaa at position 84 is His, Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln,Ser, Phe, Met, Val, Lys, Arg, Tyr or Pro; Xaa at position 85 is Ile,Leu, Arg, Asp, Val, Pro, Gln, Gly, Ser, Phe, or His; Xaa at position 86is Lys, Tyr, Leu, His, Arg, Ile, Ser, Gln, or Pro; Xaa at position 87 isAsp; Xaa at position 88 is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa atposition 89 is Asp, or Ser; Xaa at position 90 is Trp, Val, Cys, Tyr,Thr, Met, Pro, Leu, Gln, Lys, Ala, Phe, or Gly; Xaa at position 91 isAsn, Pro, Ala, Phe, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaaat position 92 is Glu, Ser, Ala, Lys, Thr, Ile, Gly, or Pro; Xaa atposition 94 is Arg, Lys, Asp, Leu, Thr, Ile, Gln, His, Ser, Ala, or Pro;Xaa at position 95 is Arg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa atposition 96 is Lys, Asn, Thr, Leu, Gln, Arg, His, Glu, Ser, Ala or Trp;Xaa at position 97 is Leu, Ile, Arg, Asp, or Met; Xaa at position 98 isThr, Val, Gln, Tyr, Glu, His, Ser, or Phe; Xaa at position 99 is Phe,Ser, Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa atposition 100 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; Xaa at position101 is Leu, Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa atposition 102 is Lys; Xaa at position 103 is Thr, Ser, Asn, Ile, Trp,Lys, or Pro; Xaa at position 104 is Leu, Ser, Pro, Ala, Glu, Cys, Asp,or Tyr; Xaa at position 105 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, orArg; Xaa at position 106 is Asn, Ala, Pro, Leu, His, Val, or Gln; Xaa atposition 107 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly; Xaa atposition 108 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, orCys; Xaa at position 109 is Ala, Met, Glu, His, Ser, Pro, Tyr, orLeu;wherein from one to three of the amino acids designated by Xaa aredifferent from the corresponding native amino acids of (1-133) humaninterleukin-3; and said mutant human interleukin-3 polypeptide has atleast three times greater cell proliferative activity than native humaninterleukin-3 wherein from one to three of the amino acids designated byXaa are different from the corresponding amino acids of native (1-133)human interleukin-3; and said mutant human interleukin-3 polypeptide hasat least three times greater cell proliferative activity than nativehuman interleukin-3 in at least one assay selected from the groupconsisting of: AML cell proliferation, TF-1 cell proliferation andMethylcellulose assay; and (b) a polypeptide comprising an N-terminalmethionine residue, alanine residue or methionine-alanine di-peptideimmediately preceding said sequence according to (a).
 8. The methodaccording to claim 7, wherein said mutant human interleukin-3polypeptide has at least ten times greater cell proliferative activitythan native human interleukin-3.
 9. The method according to claim 7,wherein said mutant human interleukin-3 polypeptide is selected from thegroup consisting of:(a) a polypeptide having an amino acid sequenceof(i) (residues 3-113 of SEQ ID NO:66); (ii) (residues 3-113 of SEQ IDNO:67); (iii) (residues 3-113 of SEQ ID NO:69); or (iv) (SEQ ID NO:218);and (b) a polypeptide comprising an N-terminal methionine residue,alanine residue or methionine-alanine di-peptide immediately precedingsaid sequence according to (a).
 10. The method according to claim 9,wherein said mutant human interleukin-3 polypeptide has at least tentimes greater cell proliferative activity than native humaninterleukin-3.
 11. The method according to claim 7, wherein in saidmutant human interleukin-3 (hIL-3) sequence the amino acids which differfrom the corresponding residue in native human interleukin-3 areselected from the group consisting of:position 28 wherein Xaa is Gly,Asp, Ser, Ile, Leu, Met, Tyr, or Ala; position 31 wherein Xaa is Gln,Val, Met or Asn; position 32 wherein Xaa is Asp, Ser, Ala, Gln, His orVal; position 36 wherein Xaa is Glu or Asp; position 37 wherein Xaa isAsn, Pro or Thr; position 48 wherein Xaa is Asn or Pro; position 62wherein Xaa is Ser, or Pro; position 68 wherein Xaa is Leu, Trp, Asp,Asn, Glu, His, Phe, Ser or Tyr; position 81 wherein Xaa is His, Arg,Thr, Asn or Ser; position 84 wherein Xaa is His, Ile, Leu, Ala, Arg,Gln, Lys, Met, Ser, Tyr or Val; position 86 wherein Xaa is Lys or Arg;position 87 wherein Xaa is Asp; position 91 wherein Xaa is Asn, or Pro;position 94 wherein Xaa is Arg, Ala, or Ser; position 102 wherein Xaa isLys; position 107 wherein Xaa is Ala, or Ile; position 108 wherein Xaais Gln, or Ile; position 109 wherein Xaa is Ala, Met or Glu.
 12. Themethod according to claim 11, wherein said mutant human interleukin-3polypeptide has at least ten times greater cell proliferative activitythan native human interleukin-3.
 13. A method of treating a patienthaving an immunodeficiency or hematopoietic disorder comprisingadministering to said patient, a therapeutically effective amount of amutant human interleukin-3 (hIL-3) polypeptide comprising a modifiedhIL-3 amino acid sequence selected from the group consisting of:(a) asequence of (SEQ ID NO:21)wherein; Xaa at position 3 is Ser, Gly, Asp,Met, or Gln; Xaa at position 4 is Asn, His, or Ile; Xaa at position 5 isMet or Ile; Xaa at position 7 is Asp or Glu; Xaa at position 9 is Ile,Ala, Leu, or Gly; Xaa at position 10 is Ile, Val, or Leu; Xaa atposition 11 is Thr, His, Gln, or Ala; Xaa at position 12 is His or Ala;Xaa at position 15 is Gln, Asn, or Val; Xaa at position 16 is Pro, Gly,or Gln; Xaa at position 17 is Pro, Asp, Gly, or Gln; Xaa at position 18is Leu, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 19 is Pro orGlu; Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Ala, Arg, Gln, Glu,Ile, Phe, Thr or Met; Xaa at position 21 is Leu, Ala, Asn, Pro, Gln, orVal; Xaa at position 23 is Phe, Ser, Pro, or Trp; Xaa at position 24 isAsn or Ala; Xaa at position 28 is Gly, Asp, Ser, Cys, Ala, Asn, Ile,Leu, Met Tyr or Arg; Xaa at position 30 is Asp or Glu; Xaa at position31 is Gln, Val, Met, Leu, Thr, Ala, Asn, Glu, Ser or Lys; Xaa atposition 32 is Asp, Phe, Ser, Thr, Ala, Asn, Gln, Glu, His, Ile, Lys,Tyr, Val or Cys; Xaa at position 36 is Glu, Ala, Asn, Ser or Asp; Xaa atposition 37 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 40is Arg or Ala; Xaa at position 41 is Arg, Thr, Val, Leu, or Gly; Xaa atposition 42 is Pro, Gly, Ser, Gln, Ala, Arg, Asn, Glu, Leu, Thr, Val orLys; Xaa at position 46 is Ala or Ser; Xaa at position 48 is Asn, Pro,Thr, or Ile; Xaa at position 49 is Arg or Lys; Xaa at position 50 is Alaor Asn; Xaa at position 51 is Val or Thr; Xaa at position 52 is Lys orArg; Xaa at position 53 is Ser, Phe, or His; Xaa at position 54 is Leu,Ile, Phe, or His; Xaa at position 55 is Gln, Ala, Pro, Thr, Glu, Arg, orGly; Xaa at position 57 is Ala, Pro, or Arg; Xaa at position 58 is Ser,Glu, Arg, or Asp; Xaa at position 59 is Ala or Leu; Xaa at position 62is Ser, Val, Ala, Asn, Glu, Pro, or Gly; Xaa at position 63 is Ile orLeu; Xaa at position 65 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp;Xaa at position 18 is Leu, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa atposition 19 is Pro or Glu; Xaa at position 20 is Leu, Val, Gly, Ser,Lys, Ala, Arg, Gln, Glu, Ile, Phe, Thr or Met; Xaa at position 21 isLeu, Ala, Asn, Pro, Gln, or Val; Xaa at position 23 is Phe, Ser, Pro, orTrp; Xaa at position 24 is Asn or Ala; Xaa at position 28 is Gly, Asp,Ser, Cys, Ala, Asn, Ile, Leu, Met Tyr or Arg; Xaa at position 30 is Aspor Glu; Xaa at position 31 is Gln, Val, Met, Leu, Thr, Ala, Asn, Glu,Ser or Lys; Xaa at position 32 is Asp, Phe, Ser, Thr, Ala, Asn, Gln,Glu, His, Ile, Lys, Tyr, Val or Cys; Xaa at position 36 is Glu, Ala,Asn, Ser or Asp; Xaa at position 37 is Asn, Arg, Met, Pro, Ser, Thr, orHis; Xaa at position 40 is Arg or Ala; Xaa at position 41 is Arg, Thr,Val, Leu, or Gly; Xaa at position 42 is Pro, Gly, Ser, Gln, Ala, Arg,Asn, Glu, Leu, Thr, Val or Lys; Xaa at position 46 is Ala or Ser; Xaa atposition 48 is Asn, Pro, Thr, or Ile; Xaa at position 49 is Arg or Lys;Xaa at position 50 is Ala or Asn; Xaa at position 51 is Val or Thr; Xaaat position 52 is Lys or Arg; Xaa at position 53 is Ser, Phe, or His;Xaa at position 54 is Leu, Ile, Phe, or His; Xaa at position 55 is Gln,Ala, Pro, Thr, Glu, Arg, or Gly; Xaa at position 57 is Ala, Pro, or Arg;Xaa at position 58 is Ser, Glu, Arg, or Asp; Xaa at position 59 is Alaor Leu; Xaa at position 62 is Ser, Val, Ala, Asn, Glu, Pro, or Gly; Xaaat position 63 is Ile or Leu; Xaa at position 65 is Lys, Thr, Gly, Asn,Met, Arg, Ile, or Asp; Xaa at position 66 is Asn, Gly, Glu, or Arg; Xaaat position 68 is Leu, Gln, Trp, Arg, Asp, Ala, Asn, Glu, His, Ile, Met,Phe, Ser, Thr, Tyr or Val; Xaa at position 69 is Pro or Thr; Xaa atposition 71 is Leu or Val; Xaa at position 73 is Leu or Ser; Xaa atposition 74 is Ala or Trp; Xaa at position 77 is Ala or Pro; Xaa atposition 79 is Thr, Asp, Ser, Pro, Ala, Leu, or Arg; Xaa at position 81is His, Pro, Arg, Val, Leu, Gly, Asn, Phe, Ser or Thr; Xaa at position82 is Pro or Tyr; Xaa at position 83 is Ile or Val; Xaa at position 84is His, Ile, Asn, Leu, Ala, Thr, Arg, Gln, Lys, Met, Ser, Tyr, Val orPro; Xaa at position 85 is Ile, Leu, or Val; Xaa at position 86 is Lys,Arg, Ile, Gln, Pro, or Ser; Xaa at position 87 is Asp; Xaa at position90 is Trp or Leu; Xaa at position 91 is Asn, Pro, Ala, Ser, Trp, Gln,Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 92 is Glu, or Gly; Xaaat position 94 is Arg, Ala, or Ser; Xaa at position 95 is Arg, Thr, Glu,Leu, or Ser; Xaa at position 98 is Thr, Val, or Gln; Xaa at position 100is Tyr or Trp; Xaa at position 101 is Leu or Ala; Xaa at position 102 isLys; Xaa at position 103 is Thr or Ser; Xaa at position 106 is Asn, Pro,Leu, His, Val, or Gln; Xaa at position 107 is Ala, Ser, Ile, Asn, Pro,Asp, or Gly; Xaa at position 108 is Gln, Ser, Met, Trp, Arg, Phe, Pro,His, Ile, Tyr, or Cys; Xaa at position 109 is Ala, Met, Glu, His, Ser,Pro, Tyr, or Leu;wherein from one to three of the amino acids designatedby Xaa are different from the corresponding amino acids of native(1-133) human interleukin-3; and said mutant human interleukin-3polypeptide has at least three times greater cell proliferative activitythan native human interleukin-3 in at least one assay selected from thegroup consisting of: AML cell proliferation, TF-1 cell proliferation andMethylcellulose assay; and (b) a polypeptide comprising an N-terminalmethionine residue, alanine residue or methionine-alanine di-peptideimmediately preceding said sequence according to (a).
 14. The methodaccording to claim 13, wherein said mutant human interleukin-3polypeptide has at least ten times greater cell proliferative activitythan native human interleukin-3.
 15. The method according to claim 1, 2,5, 6, 3, 4, 7, 8, 9, 10, 13, 14, 11 or 12 wherein said immunodeficiencyor hematopoietic disorder is the result of a viral infection, bacterialinfection or fungal infection.
 16. The method according to claim 1, 2,5, 6, 3, 4, 7, 8, 9, 10, 13, 14, 11 or 12 wherein said immunodeficiencyor hematopoietic disorder is the result of cancer radiation therapy orchemotherapy.
 17. The method according to claim 1, 2, 5, 6, 3, 4, 7, 8,9, 10, 13, 14, 11 or 12 wherein said immunodeficiency is the result ofthe treatment of a patient with a drug which causes bone marrowsuppression.
 18. A method of treating a patient comprising the stepsof:(i) administering to said patient, an amount of a mutant humaninterleukin-3 (IL-3) polypeptide, effective to promote the proliferationand/or differentiation of hematopoietic cells in said patient, whereinsaid mutant human interleukin-3 (hIL-3) polypeptide comprises a modifiedhIL-3 amino acid sequence selected from the group consisting of: (a) asequence of (SEQ ID NO:15)wherein; Xaa at position 17 is Ser, Lys, Gly,Asp, Met, Gln, or Arg; Xaa at position 18 is Asn, His, Leu, Ile, Phe,Arg, or Gln; Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala; Xaa atposition 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser orVal; Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln,Leu, Val or Gly; Xaa at position 23 is Ile, Val, Ala, Leu, Gly, Trp,Lys, Phe, Ser, or Arg; Xaa at position 24 is Ile, Gly, Val, Arg, Ser,Phe, or Leu; Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp; Xaa atposition 27 is Leu, Gly, Arg, Thr, Ser, or Ala; Xaa at position 28 isLys, Arg, Leu, Gln, Gly, Pro, Val or Trp; Xaa at position 29 is Gln,Asn, Leu, Pro, Arg, or Val; Xaa at position 30 is Pro, His, Thr, Gly,Asp, Gln, Ser, Leu, or Lys; Xaa at position 31 is Pro, Asp, Gly, Ala,Arg, Leu, or Gln; Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly,Ala, or Glu; Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu; Xaaat position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe,Ile or Met; Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;Xaa at position 36 is Asp, Leu, or Val; Xaa at position 37 is Phe, Ser,Pro, Trp, or Ile; Xaa at position 38 is Asn, or Ala; Xaa at position 40is Leu, Trp, or Arg; Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met,or Pro; Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu,Val, Glu, Phe, Tyr, Ile, Met or Ala; Xaa at position 43 is Glu, Asn,Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser; Xaa at position44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp,Asn, Arg, Ser, Ala, Ile, Glu or His; Xaa at position 46 is Asp, Phe,Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaaat position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His; Xaa at position48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val orAsn; Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile,Val, His, Phe, Met or Gln; Xaa at position 51 is Asn, Arg, Met, Pro,Ser, Thr, or His; Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, orThr; Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, orMet; Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys,His, Ala or Leu; Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala,Tyr, Phe, Leu, Val or Lys; Xaa at position 57 is Asn or Gly; Xaa atposition 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys; Xaa at position 59is Glu, Tyr, His, Leu, Pro, or Arg; Xaa at position 60 is Ala, Ser, Pro,Tyr, Asn, or Thr; Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, orSer; Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val; Xaa atposition 64 is Ala, Asn, Pro, Ser, or Lys; Xaa at position 65 is Val,Thr, Pro, His, Leu, Phe, or Ser; Xaa at position 66 is Lys, Ile, Arg,Val, Asn, Glu, or Ser; Xaa at position 67 is Ser, Ala, Phe, Val, Gly,Asn, Ile, Pro, or His; Xaa at position 68 is Leu, Val, Trp, Ser, Ile,Phe, Thr, or His; Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg,Trp, Gly, or Leu; Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, orAsn; Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa atposition 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala; Xaa at position 75 isGlu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu; Xaa at position 76is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp; Xaa at position 77 isIle, Ser, Arg, Thr, or Leu; Xaa at position 78 is Leu, Ala, Ser, Glu,Phe, Gly, or Arg; Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile,Gly, or Asp; Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, orArg; Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr,Ser, Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 83 is Pro, Ala,Thr, Trp, Arg, or Met; Xaa at position 84 is Cys, Glu, Gly, Arg, Met, orVal; Xaa at position 85 is Leu, Asn, Val, or Gln; Xaa at position 86 isPro, Cys, Arg, Ala, or Lys; Xaa at position 87 is Leu, Ser, Trp, or Gly;Xaa at position 88 is Ala, Lys, Arg, Val, or Trp; Xaa at position 89 isThr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 90 isAla, Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 91 is Ala,Pro, Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 92 is Pro, Phe,Arg, Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 93 is Thr,Asp, Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 94 is Arg, Ile,Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro; Xaa at position 95 isHis, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe,Ile, or Tyr; Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaaat position 97 is Ile, Val, Lys, Ala, or Asn; Xaa at position 98 is His,Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg,Tyr or Pro; Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln,Gly, Ser, Phe, or His; Xaa at position 100 is Lys, Tyr, Leu, His, Arg,Ile, Ser, Gln, or Pro; Xaa at position 101 is Asp; Xaa at position 102is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 103 is Asp, orSer; Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln,Lys, Ala, Phe, or Gly; Xaa at position 105 is Asn, Pro, Ala, Phe, Ser,Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 106 is Glu,Ser, Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 108 is Arg, Lys,Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro; Xaa at position 109 isArg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 110 is Lys,Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, Ala, or Trp; Xaa atposition 111 is Leu, Ile, Arg, Asp, or Met; Xaa at position 112 is Thr,Val, Gln, Tyr, Glu, His, Ser, or Phe; Xaa at position 113 is Phe, Ser,Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 115 is Leu,Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 116 isLys; Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa atposition 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa atposition 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa atposition 120 is Asn, Ala, Pro, Leu, His, Val, or Gln; Xaa at position121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly; Xaa at position 122 isGln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa atposition 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;wherein fromone to three of the amino acids designated by Xaa are different from thecorresponding amino acids of native (1-133) human interleukin-3; andwherein from 1 to 14 amino acids are optionally deleted from theN-terminus and/or from 1 to 15 amino acids are optionally deleted fromthe C-terminus; and said mutant human interleukin-3 polypeptide has atleast three times greater cell proliferative activity than native humaninterleukin-3 in at least one assay selected from the group consistingof: AML cell proliferation, TF-1 cell proliferation and Methylcelluloseassay; and (b) a polypeptide comprising an N-terminal methionineresidue, alanine residue or methionine-alanine di-peptide immediatelypreceding said sequence according to (a);(ii) removing hematopoieticcells from said patient; (iii) administering to said patient cancerradiation therapy or chemotherapy; and (iv) returning said hematopoieticcells to said patient.
 19. The method according to claim 18, whereinsaid mutant human interleukin-3 polypeptide has at least ten timesgreater cell proliferative activity than native human interleukin-3. 20.The method according to claim 18, wherein in said mutant humaninterleukin-3 (hIL-3) sequence the amino acids which differ from thecorresponding residue in native human interleukin-3 are selected fromthe group consisting of:position 42 wherein Xaa is Gly, Asp, Ser, Ile,Leu, Met, Tyr, or Ala; position 45 wherein Xaa is Gln, Val, Met or Asn;position 46 wherein Xaa is Asp, Ser, Gln, His or Val; position 50wherein Xaa is Glu or Asp; position 51 wherein Xaa is Asn, Pro or Thr;position 62 wherein Xaa is Asn or Pro; position 76 wherein Xaa is Ser,or Pro; position 82 wherein Xaa is Leu, Trp, Asp, Asn Glu, His, Phe, Seror Tyr; position 95 wherein Xaa is His, Arg, Thr, Asn or Ser; position98 wherein Xaa is His, Ile, Leu, Ala, Gln, Lys, Met, Ser, Tyr or Val;position 100 wherein Xaa is Lys or Arg; position 101 wherein Xaa is Asp;position 105 wherein Xaa is Asn, or Pro; position 108 wherein Xaa isArg, Ala, or Ser; position 116 wherein Xaa is Lys; position 121 whereinXaa is Ala, or Ile; position 122 wherein Xaa is Gln, or Ile; position123 wherein Xaa is Ala, Met or Glu.
 21. The method according to claim20, wherein said mutant human interleukin-3 polypeptide has at least tentimes greater cell proliferative activity than native humaninterleukin-3.
 22. A method of treating a patient comprising the stepsof:(i) administering to said patient, an amount of a mutant humaninterleukin-3 (IL-3) polypeptide, effective to promote the proliferationand/or differentiation of hematopoietic cells in said patient, whereinsaid mutant human interleukin-3 (hIL-3) polypeptide comprises a modifiedhIL-3 amino acid sequence selected from the group consisting of: (a) asequence of(SEQ ID NO:17)wherein; Xaa at position 17 is Ser, Gly, Asp,Met, or Gln; Xaa at position 18 is Asn, His, or Ile; Xaa at position 19is Met or Ile; Xaa at position 21 is Asp or Glu; Xaa at position 23 isIle, Ala, Leu, or Gly; Xaa at position 24 is Ile, Val, or Leu; Xaa atposition 25 is Thr, His, Gln, or Ala; Xaa at position 26 is His or Ala;Xaa at position 29 is Gln, Asn, or Val; Xaa at position 30 is Pro, Gly,or Gln; Xaa at position 31 is Pro, Asp, Gly, or Gln; Xaa at position 32is Leu, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 33 is Pro orGlu; Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Ala, Arg, Gln, Glu,Ile, Phe, Thr or Met; Xaa at position 35 is Leu, Ala, Asn, Pro, Gln, orVal; Xaa at position 37 is Phe, Ser, Pro, or Trp; Xaa at position 38 isAsn or Ala; Xaa at position 42 is Gly, Asp, Ser, Cys, Ala, Asn, Ile,Leu, Met, Tyr or Arg; Xaa at position 44 is Asp or Glu; Xaa at position45 is Gln, Val, Met, Leu, Thr, Ala, Asn, Glu, Ser or Lys; Xaa atposition 46 is Asp, Phe, Ser, Thr, Ala, Asn, Gln, Glu, His, Ile, Lys,Tyr, Val or Cys; Xaa at position 50 is Glu, Ala, Asn, Ser or Asp; Xaa atposition 51 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 54is Arg or Ala; Xaa at position 55 is Arg, Thr, Val, Leu, or Gly; Xaa atposition 56 is Pro, Gly, Ser, Gln, Ala, Arg, Asn, Glu, Leu, Thr, Val orLys; Xaa at position 60 is Ala or Ser; Xaa at position 62 is Asn, Pro,Thr, or Ile; Xaa at position 63 is Arg or Lys; Xaa at position 64 is Alaor Asn; Xaa at position 65 is Val or Thr; Xaa at position 66 is Lys orArg; Xaa at position 67 is Ser, Phe, or His; Xaa at position 68 is Leu,Ile, Phe, or His; Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, orGly; Xaa at position 71 is Ala, Pro, or Arg; Xaa at position 72 is Ser,Glu, Arg, or Asp; Xaa at position 73 is Ala or Leu; Xaa at position 76is Ser, Val, Ala, Asn, Glu, Pro, or Gly; Xaa at position 77 is Ile orLeu; Xaa at position 79 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp;Xaa at position 80 is Asn, Gly, Glu, or Arg; Xaa at position 82 is Leu,Gln, Trp, Arg, Asp, Ala, Asn, Glu, His, Ile, Met, Phe, Ser, Thr, Tyr orVal; Xaa at position 83 is Pro or Thr; Xaa at position 85 is Leu or Val;Xaa at position 87 is Leu or Ser; Xaa at position 88 is Ala or Trp; Xaaat position 91 is Ala or Pro; Xaa at position 93 is Thr, Asp, Ser, Pro,Ala, Leu, or Arg; Xaa at position 95 is His, Pro, Arg, Val, Leu, Gly,Asn, Phe, Ser or Thr; Xaa at position 96 is Pro or Tyr; Xaa at position97 is Ile or Val; Xaa at position 98 is His, Ile, Asn, Leu, Ala, Thr,Arg, Gln, Lys, Met, Ser, Tyr, Val or Pro; Xaa at position 99 is Ile,Leu, or Val; Xaa at position 100 is Lys, Arg, Ile, Gln, Pro, or Ser; Xaaat position 101 is Asp; Xaa at position 104 is Trp or Leu; Xaa atposition 105 is Asn, Pro, Ala, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp,or His; Xaa at position 106 is Glu or Gly; Xaa at position 108 is Arg,Ala, or Ser; Xaa at position 109 is Arg, Thr, Glu, Leu, or Ser; Xaa atposition 112 is Thr, Val, or Gln; Xaa at position 114 is Tyr or Trp; Xaaat position 115 is Leu or Ala; Xaa at position 116 is Lys; Xaa atposition 117 is Thr or Ser; Xaa at position 120 is Asn, Pro, Leu, His,Val, or Gln; Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Asp, orGly; Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile,Tyr, or Cys; Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr,or Leu;wherein from one to three of the amino acids designated by Xaaare different from the corresponding amino acids of native (1-133) humaninterleukin-3; and wherein from 1 to 14 amino acids are optionallydeleted from the N-terminus and/or from 1 to 15 amino acids areoptionally deleted from the C-terminus; and said mutant humaninterleukin-3 polypeptide has at least three times greater cellproliferative activity than native human interleukin-3 in at least oneassay selected from the group consisting of: AML cell proliferation,TF-1 cell proliferation and Methylcellulose assay; and (b) a polypeptidecomprising an N-terminal methionine residue, alanine residue ormethionine-alanine di-peptide immediately preceding said sequenceaccording to (a);(ii) removing hematopoietic cells from said patient;(iii) administering to said patient cancer radiation therapy orchemotherapy; and (iv) returning said hematopoietic cells to saidpatient.
 23. The method according to claim 22, wherein said mutant humaninterleukin-3 polypeptide has at least ten times greater cellproliferative activity than native human interleukin-3.
 24. A method oftreating a patient comprising the steps of:(i) administering to saidpatient, an amount of a mutant human interleukin-3 (IL-3) polypeptide,effective to promote the proliferation and/or differentiation ofhematopoietic cells in said patient, wherein said mutant humaninterleukin-3 (hIL-3) polypeptide comprises a modified hIL-3 amino acidsequence selected from the group consisting of: (a) a sequence of(SEQ IDNO:19)wherein; Xaa at position 3 is Ser, Lys, Gly, Asp, Met, Gln, orArg; Xaa at position 4 is Asn, His, Leu, Ile, Phe, Arg, or Gln; Xaa atposition 5 is Met, Phe, Ile, Arg, Gly, Ala, or Cys; Xaa at position 6 isIle, Cys, Gln, Glu, Arg, Pro, or Ala; Xaa at position 7 is Asp, Phe,Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val; Xaa at position 8 isGlu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val, or Gly; Xaa atposition 9 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg; Xaaat position 10 is Ile, Gly, Val, Arg, Ser, Phe, or Leu; Xaa at position11 is Thr, His, Gly, Gln, Arg, Pro, or Ala; Xaa at position 12 is His,Thr, Phe, Gly, Arg, Ala, or Trp; Xaa at position 13 is Leu, Gly, Arg,Thr, Ser, or Ala; Xaa at position 14 is Lys, Arg, Leu, Gln, Gly, Pro,Val or Trp; Xaa at position 15 is Gln, Asn, Leu, Pro, Arg, or Val; Xaaat position 16 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys; Xaa atposition 17 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa at position 18is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 19 is Pro,Leu, Gln, Ala, Thr, or Glu; Xaa at position 20 is Leu, Val, Gly, Ser,Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaa at position 21 isLeu, Ala, Gly, Asn, Pro, Gln, or Val; Xaa at position 22 is Asp, Leu, orVal; Xaa at position 23 is Phe, Ser, Pro, Trp, or Ile; Xaa at position24 is Asn, or Ala; Xaa at position 26 is Leu, Trp, or Arg; Xaa atposition 27 is Asn, Cys, Arg, Leu, His, Met, Pro; Xaa at position 28 isGly, Asp, Ser, Cys, Ala, Lys, Asn, Thr, Leu, Val, Glu, Phe, Tyr, Ile orMet; Xaa at position 29 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln,Arg, Thr, Gly or Ser; Xaa at position 30 is Asp, Ser, Leu, Arg, Lys,Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro; Xaa at position 31 is Gln,Pro, Phe, Val, Met, Leu, Thr, Lys, Asp, Asn, Arg, Ser, Ala, Ile, Glu,His or Trp; Xaa at position 32 is Asp, Phe, Ser, Thr, Cys, Glu, Asn,Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaa at position 33 is Ile,Gly, Val, Ser, Arg, Pro, or His; Xaa at position 34 is Leu, Ser, Cys,Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn; Xaa at position35 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa at position 36 isGlu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met orGln; Xaa at position 37 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa atposition 38 is Asn, His, Arg, Leu, Gly, Ser, or Thr; Xaa at position 39is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met; Xaa at position 40 isArg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu; Xaa atposition 41 is Arg, Thr, Val, Ser, Leu, or Gly; Xaa at position 42 isPro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val orLys; Xaa at position 43 is Asn or Gly; Xaa at position 44 is Leu, Ser,Asp, Arg, Gln, Val, or Cys; Xaa at position 45 is Glu, Tyr, His, Leu,Pro, or Arg; Xaa at position 46 is Ala, Ser, Pro, Tyr, Asn, or Thr; Xaaat position 47 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser; Xaa at position48 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile; Xaa at position 49 isArg, Tyr, Trp, Lys, Ser, His, Pro, or Val; Xaa at position 50 is Ala,Asn, Pro, Ser, or Lys; Xaa at position 51 is Val, Thr, Pro, His, Leu,Phe, or Ser; Xaa at position 52 is Lys, Ile, Arg, Val, Asn, Glu, or Ser;Xaa at position 53 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His;Xaa at position 54 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His; Xaa atposition 55 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu; Xaa atposition 56 is Asn, Leu, Val, Trp, Pro, or Ala; Xaa at position 57 isAla, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn; Xaa at position 58is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp; Xaa at position 59 is Ala,Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa at position 60 is Ile, Met,Thr, Pro, Arg, Gly, Ala; Xaa at position 61 is Glu, Lys, Gly, Asp, Pro,Trp, Arg, Ser, Gln, or Leu; Xaa at position 62 is Ser, Val, Ala, Asn,Trp, Glu, Pro, Gly, or Asp; Xaa at position 63 is Ile, Ser, Arg, Thr, orLeu; Xaa at position 64 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg; Xaa atposition 65 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp; Xaa atposition 66 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg; Xaa atposition 67 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys; Xaa atposition 68 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser,Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 69 is Pro, Ala, Thr,Trp, Arg, or Met; Xaa at position 70 is Cys, Glu, Gly, Arg, Met, or Val;Xaa at position 71 is Leu, Asn, Val, or Gln; Xaa at position 72 is Pro,Cys, Arg, Ala, or Lys; Xaa at position 73 is Leu, Ser, Trp, or Gly; Xaaat position 74 is Ala, Lys, Arg, Val, or Trp; Xaa at position 75 is Thr,Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 76 is Ala,Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 77 is Ala, Pro,Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 78 is Pro, Phe, Arg,Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 79 is Thr, Asp,Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 80 is Arg, Ile, Ser,Glu, Leu, Val, Gln, Lys, His, Ala or Pro; Xaa at position 81 is His,Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile orTyr; Xaa at position 82 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaa atposition 83 is Ile, Val, Lys, Ala, or Asn; Xaa at position 84 is His,Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg,Tyr or Pro; Xaa at position 85 is Ile, Leu, Arg, Asp, Val, Pro, Gln,Gly, Ser, Phe, or His; Xaa at position 86 is Lys, Tyr, Leu, His, Arg,Ile, Ser, Gln, or Pro; Xaa at position 87 is Asp; Xaa at position 88 isGly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 89 is Asp, or Ser;Xaa at position 90 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys,Ala, Phe, or Gly; Xaa at position 91 is Asn, Pro, Ala, Phe, Ser, Trp,Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 92 is Glu, Ser,Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 94 is Arg, Lys, Asp,Leu, Thr, Ile, Gln, His, Ser, Ala, or Pro; Xaa at position 95 is Arg,Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 96 is Lys, Asn,Thr, Leu, Gln, Arg, His, Glu, Ser, Ala or Trp; Xaa at position 97 isLeu, Ile, Arg, Asp, or Met; Xaa at position 98 is Thr, Val, Gln, Tyr,Glu, His, Ser, or Phe; Xaa at position 99 is Phe, Ser, Cys, His, Gly,Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position 100 is Tyr,Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 101 is Leu, Asn, Val,Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 102 is Lys; Xaa atposition 103 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa at position104 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa at position 105 isGlu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa at position 106 is Asn,Ala, Pro, Leu, His, Val, or Gln; Xaa at position 107 is Ala, Ser, Ile,Asn, Pro, Lys, Asp, or Gly; Xaa at position 108 is Gln, Ser, Met, Trp,Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa at position 109 is Ala, Met,Glu, His, Ser, Pro, Tyr, or Leu;wherein from one to three of the aminoacids designated by Xaa are different from the corresponding nativeamino acids of (1-133) human interleukin-3; and said mutant humaninterleukin-3 polypeptide has at least three times greater cellproliferative activity than native human interleukin-3 wherein from oneto three of the amino acids designated by Xaa are different from thecorresponding amino acids of native (1-133) human interleukin-3; andsaid mutant human interleukin-3 polypeptide has at least three timesgreater cell proliferative activity than native human interleukin-3 inat least one assay selected from the group consisting of: AML cellproliferation, TF-1 cell proliferation and Methylcellulose assay; and(b) a polypeptide comprising an N-terminal methionine residue, alanineresidue or methionine-alanine di-peptide immediately preceding saidsequence according to (a);(ii) removing hematopoietic cells from saidpatient; (iii) administering to said patient cancer radiation therapy orchemotherapy; and (iv) returning said hematopoietic cells to saidpatient.
 25. The method according to claim 24, wherein said mutant humaninterleukin-3 polypeptide has at least ten times greater cellproliferative activity than native human interleukin-3.
 26. The methodaccording to claim 24, wherein said mutant human interleukin-3polypeptide is selected from the group consisting of:(a) a polypeptidehaving an amino acid sequence of(i) (residues 3-113 of SEQ ID NO:66);(ii) (residues 3-113 of SEQ ID NO:67); (iii) (residues 3-113 of SEQ IDNO:69); or (iv) (SEQ ID NO:218); and (b) an N-terminal methionineresidue, alanine residue or methionine-alanine di-peptide immediatelypreceding said sequence according to (a).
 27. The method according toclaim 26, wherein said mutant human interleukin-3 polypeptide has atleast ten times greater cell proliferative activity than native humaninterleukin-3.
 28. The method according to claim 24, wherein in saidmutant human interleukin-3 (hIL-3) sequence the amino acids which differfrom the corresponding residue in native human interleukin-3 areselected from the group consisting of:position 28 wherein Xaa is Gly,Asp, Ser, Ile, Leu, Met, Tyr, or Ala; position 31 wherein Xaa is Gln,Val, Met or Asn; position 32 wherein Xaa is Asp, Ser, Ala, Gln, His orVal; position 36 wherein Xaa is Glu or Asp; position 37 wherein Xaa isAsn, Pro or Thr; position 48 wherein Xaa is Asn or Pro; position 62wherein Xaa is Ser, or Pro; position 68 wherein Xaa is Leu, Trp, Asp,Asn, Glu, His, Phe, Ser or Tyr; position 81 wherein Xaa is His, Arg,Thr, Asn or Ser; position 84 wherein Xaa is His, Ile, Leu, Ala, Arg,Gln, Lys, Met, Ser, Tyr or Val; position 86 wherein Xaa is Lys or Arg;position 87 wherein Xaa is Asp; position 91 wherein Xaa is Asn, or Pro;position 94 wherein Xaa is Arg, Ala, or Ser; position 102 wherein Xaa isLys; position 107 wherein Xaa is Ala, or Ile; position 108 wherein Xaais Gln, or Ile; position 109 wherein Xaa is Ala, Met or Glu.
 29. Themethod according to claim 28, wherein said mutant human interleukin-3polypeptide has at least ten times greater cell proliferative activitythan native human interleukin-3.
 30. A method of treating a patientcomprising the steps of:(i) administering to said patient, an amount ofa mutant human interleukin-3 (IL-3) polypeptide, effective to promotethe proliferation and/or differentiation of hematopoietic cells in saidpatient, wherein said mutant human interleukin-3 (hIL-3) polypeptidecomprises a modified hIL-3 amino acid sequence selected from the groupconsisting of: (a) a sequence of (SEQ ID NO:21)wherein; Xaa at position3 is Ser, Gly, Asp, Met, or Gln; Xaa at position 4 is Asn, His, or Ile;Xaa at position 5 is Met or Ile; Xaa at position 7 is Asp or Glu; Xaa atposition 9 is Ile, Ala, Leu, or Gly; Xaa at position 10 is Ile, Val, orLeu; Xaa at position 11 is Thr, His, Gln, or Ala; Xaa at position 12 isHis or Ala; Xaa at position 15 is Gln, Asn, or Val; Xaa at position 16is Pro, Gly, or Gln; Xaa at position 17 is Pro, Asp, Gly, or Gln; Xaa atposition 18 is Leu, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 19is Pro or Glu; Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Ala, Arg,Gln, Glu, Ile, Phe, Thr or Met; Xaa at position 21 is Leu, Ala, Asn,Pro, Gln, or Val; Xaa at position 23 is Phe, Ser, Pro, or Trp; Xaa atposition 24 is Asn or Ala; Xaa at position 28 is Gly, Asp, Ser, Cys,Ala, Asn, Ile, Leu, Met Tyr or Arg; Xaa at position 30 is Asp or Glu;Xaa at position 31 is Gln, Val, Met, Leu, Thr, Ala, Asn, Glu, Ser orLys; Xaa at position 32 is Asp, Phe, Ser, Thr, Ala, Asn, Gln, Glu, His,Ile, Lys, Tyr, Val or Cys; Xaa at position 36 is Glu, Ala, Asn, Ser orAsp; Xaa at position 37 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa atposition 40 is Arg or Ala; Xaa at position 41 is Arg, Thr, Val, Leu, orGly; Xaa at position 42 is Pro, Gly, Ser, Gln, Ala, Arg, Asn, Glu, Leu,Thr, Val or Lys; Xaa at position 46 is Ala or Ser; Xaa at position 48 isAsn, Pro, Thr, or Ile; Xaa at position 49 is Arg or Lys; Xaa at position50 is Ala or Asn; Xaa at position 51 is Val or Thr; Xaa at position 52is Lys or Arg; Xaa at position 53 is Ser, Phe, or His; Xaa at position54 is Leu, Ile, Phe, or His; Xaa at position 55 is Gln, Ala, Pro, Thr,Glu, Arg, or Gly; Xaa at position 57 is Ala, Pro, or Arg; Xaa atposition 58 is Ser, Glu, Arg, or Asp; Xaa at position 59 is Ala or Leu;Xaa at position 62 is Ser, Val, Ala, Asn, Glu, Pro, or Gly; Xaa atposition 63 is Ile or Leu; Xaa at position 65 is Lys, Thr, Gly, Asn,Met, Arg, Ile, or Asp; Xaa at position 66 is Asn, Gly, Glu, or Arg; Xaaat position 68 is Leu, Gln, Trp, Arg, Asp, Ala, Asn, Glu, His, Ile, Met,Phe, Ser, Thr, Tyr or Val; Xaa at position 69 is Pro or Thr; Xaa atposition 71 is Leu or Val; Xaa at position 73 is Leu or Ser; Xaa atposition 74 is Ala or Trp; Xaa at position 77 is Ala or Pro; Xaa atposition 79 is Thr, Asp, Ser, Pro, Ala, Leu, or Arg; Xaa at position 81is His, Pro, Arg, Val, Leu, Gly, Asn, Phe, Ser or Thr; Xaa at position82 is Pro or Tyr; Xaa at position 83 is Ile or Val; Xaa at position 84is His, Ile, Asn, Leu, Ala, Thr, Arg, Gln, Lys, Met, Ser, Tyr, Val orPro; Xaa at position 85 is Ile, Leu, or Val; Xaa at position 86 is Lys,Arg, Ile, Gln, Pro, or Ser; Xaa at position 87 is Asp; Xaa at position90 is Trp or Leu; Xaa at position 91 is Asn, Pro, Ala, Ser, Trp, Gln,Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 92 is Glu, or Gly; Xaaat position 94 is Arg, Ala, or Ser; Xaa at position 95 is Arg, Thr, Glu,Leu, or Ser; Xaa at position 98 is Thr, Val, or Gln; Xaa at position 100is Tyr or Trp; Xaa at position 101 is Leu or Ala; Xaa at position 102 isLys; Xaa at position 103 is Thr or Ser; Xaa at position 106 is Asn, Pro,Leu, His, Val, or Gln; Xaa at position 107 is Ala, Ser, Ile, Asn, Pro,Asp, or Gly; Xaa at position 108 is Gln, Ser, Met, Trp, Arg, Phe, Pro,His, Ile, Tyr, or Cys; Xaa at position 109 is Ala, Met, Glu, His, Ser,Pro, Tyr, or Leu;wherein from one to three of the amino acids designatedby Xaa are different from the corresponding amino acids of native(1-133) human interleukin-3; and said mutant human interleukin-3polypeptide has at least three times greater cell proliferative activitythan native human interleukin-3 in at least one assay selected from thegroup consisting of: AML cell proliferation, TF-1 cell proliferation andMethylcellulose assay; and (b) a polypeptide comprising an N-terminalmethionine residue, alanine residue or methionine-alanine di-peptideimmediately preceding said sequence according to (a);(ii) removinghematopoietic cells from said patient; (iii) administering to saidpatient cancer radiation therapy or chemotherapy; and (iv) returningsaid hematopoietic cells to said patient.
 31. The method according toclaim 30, wherein said mutant human interleukin-3 polypeptide has atleast ten times greater cell proliferative activity than native humaninterleukin-3.
 32. A method of treating a side effect of cancerchemotherapy or radiation therapy in a patient comprising administeringto said patient, a therapeutically effective amount of a mutant humaninterleukin-3 (hIL-3) polypeptide comprising a modified hIL-3 amino acidsequence selected from the group consisting of:(a) a sequence of (SEQ IDNO:15)wherein; Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, orArg; Xaa at position 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln; Xaa atposition 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys; Xaa at position 20is Ile, Cys, Gln, Glu, Arg, Pro, or Ala; Xaa at position 21 is Asp, Phe,Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val; Xaa at position 22is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly; Xaa atposition 23 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg; Xaaat position 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu; Xaa at position25 is Thr, His, Gly, Gln, Arg, Pro, or Ala; Xaa at position 26 is His,Thr, Phe, Gly, Arg, Ala, or Trp; Xaa at position 27 is Leu, Gly, Arg,Thr, Ser, or Ala; Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro,Val or Trp; Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val; Xaaat position 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys; Xaa atposition 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa at position 32is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 33 is Pro,Leu, Gln, Ala, Thr, or Glu; Xaa at position 34 is Leu, Val, Gly, Ser,Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaa at position 35 isLeu, Ala, Gly, Asn, Pro, Gln, or Val; Xaa at position 36 is Asp, Leu, orVal; Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile; Xaa at position38 is Asn, or Ala; Xaa at position 40 is Leu, Trp, or Arg; Xaa atposition 41 is Asn, Cys, Arg, Leu, His, Met, or Pro; Xaa at position 42is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Metor Ala; Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys,Gln, Arg, Thr, Gly or Ser; Xaa at position 44 is Asp, Ser, Leu, Arg,Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro; Xaa at position 45 isGln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala,Ile, Glu or His; Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu,Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaa at position 47 isIle, Gly, Val, Ser, Arg, Pro, or His; Xaa at position 48 is Leu, Ser,Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn; Xaa atposition 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa atposition 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val,His, Phe, Met or Gln; Xaa at position 51 is Asn, Arg, Met, Pro, Ser,Thr, or His; Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His,Ala or Leu; Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly; Xaaat position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr,Phe, Leu, Val or Lys; Xaa at position 57 is Asn or Gly; Xaa at position58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys; Xaa at position 59 is Glu,Tyr, His, Leu, Pro, or Arg; Xaa at position 60 is Ala, Ser, Pro, Tyr,Asn, or Thr; Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile; Xaa atposition 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val; Xaa atposition 64 is Ala, Asn, Pro, Ser, or Lys; Xaa at position 65 is Val,Thr, Pro, His, Leu, Phe, or Ser; Xaa at position 66 is Lys, Ile, Arg,Val, Asn, Glu, or Ser; Xaa at position 67 is Ser, Ala, Phe, Val, Gly,Asn, Ile, Pro, or His; Xaa at position 68 is Leu, Val, Trp, Ser, Ile,Phe, Thr, or His; Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg,Trp, Gly, or Leu; Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, orAsn; Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa atposition 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala; Xaa at position 75 isGlu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu; Xaa at position 76is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp; Xaa at position 77 isIle, Ser, Arg, Thr, or Leu; Xaa at position 78 is Leu, Ala, Ser, Glu,Phe, Gly, or Arg; Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile,Gly, or Asp; Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, orArg; Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr,Ser, Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 83 is Pro, Ala,Thr, Trp, Arg, or Met; Xaa at position 84 is Cys, Glu, Gly, Arg, Met, orVal; Xaa at position 85 is Leu, Asn, Val, or Gln; Xaa at position 86 isPro, Cys, Arg, Ala, or Lys; Xaa at position 87 is Leu, Ser, Trp, or Gly;Xaa at position 88 is Ala, Lys, Arg, Val, or Trp; Xaa at position 89 isThr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 90 isAla, Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 91 is Ala,Pro, Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 92 is Pro, Phe,Arg, Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 93 is Thr,Asp, Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 94 is Arg, Ile,Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro; Xaa at position 95 isHis, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe,Ile, or Tyr; Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaaat position 97 is Ile, Val, Lys, Ala, or Asn; Xaa at position 98 is His,Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg,Tyr or Pro; Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln,Gly, Ser, Phe, or His; Xaa at position 100 is Lys, Tyr, Leu, His, Arg,Ile, Ser, Gln, or Pro; Xaa at position 101 is Asp; Xaa at position 102is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 103 is Asp, orSer; Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln,Lys, Ala, Phe, or Gly; Xaa at position 105 is Asn, Pro, Ala, Phe, Ser,Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 106 is Glu,Ser, Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 108 is Arg, Lys,Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro; Xaa at position 109 isArg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 110 is Lys,Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, Ala, or Trp; Xaa atposition 111 is Leu, Ile, Arg, Asp, or Met; Xaa at position 112 is Thr,Val, Gln, Tyr, Glu, His, Ser, or Phe; Xaa at position 113 is Phe, Ser,Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 115 is Leu,Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 116 isLys; Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa atposition 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa atposition 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa atposition 120 is Asn, Ala, Pro, Leu, His, Val, or Gln; Xaa at position121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly; Xaa at position 122 isGln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa atposition 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;wherein fromone to three of the amino acids designated by Xaa are different from thecorresponding amino acids of native (1-133) human interleukin-3; andwherein from 1 to 14 amino acids are optionally deleted from theN-terminus and/or from 1 to 15 amino acids are optionally deleted fromthe C-terminus; and said mutant human interleukin-3 polypeptide has atleast three times greater cell proliferative activity than native humaninterleukin-3 in at least one assay selected from the group consistingof: AML cell proliferation, TF-1 cell proliferation and Methylcelluloseassay; and (b) a polypeptide comprising an N-terminal methionineresidue, alanine residue or methionine-alanine di-peptide immediatelypreceding said sequence according to (a).
 33. The method according toclaim 32, wherein said mutant human interleukin-3 polypeptide has atleast ten times greater cell proliferative activity than native humaninterleukin-3.
 34. The method according to claim 32 wherein in saidmutant human interleukin-3 (hIL-3) sequence the amino acids which differfrom the corresponding residue in native human interleukin-3 areselected from the group consisting of:position 42 wherein Xaa is Gly,Asp, Ser, Ile, Leu, Met, Tyr, or Ala; position 45 wherein Xaa is Gln,Val, Met or Asn; position 46 wherein Xaa is Asp, Ser, Gln, His or Val;position 50 wherein Xaa is Glu or Asp; position 51 wherein Xaa is Asn,Pro or Thr; position 62 wherein Xaa is Asn or Pro; position 76 whereinXaa is Ser, or Pro; position 82 wherein Xaa is Leu, Trp, Asp, Asn Glu,His, Phe, Ser or Tyr; position 95 wherein Xaa is His, Arg, Thr, Asn orSer; position 98 wherein Xaa is His, Ile, Leu, Ala, Gln, Lys, Met, Ser,Tyr or Val; position 100 wherein Xaa is Lys or Arg; position 101 whereinXaa is Asp; position 105 wherein Xaa is Asn, or Pro; position 108wherein Xaa is Arg, Ala, or Ser; position 116 wherein Xaa is Lys;position 121 wherein Xaa is Ala, or Ile; position 122 wherein Xaa isGln, or Ile; position 123 wherein Xaa is Ala, Met or Glu.
 35. The methodaccording to claim 34, wherein said mutant human interleukin-3polypeptide has at least ten times greater cell proliferative activitythan native human interleukin-3.
 36. A method of treating a side effectof cancer chemotherapy or radiation therapy in a patient comprisingadministering to said patient, a therapeutically effective amount of amutant human interleukin-3 (hIL-3) polypeptide comprising a modifiedhIL-3 amino acid sequence selected from the group consisting of:(a) asequence of (SEQ ID NO:17)wherein; Xaa at position 17 is Ser, Gly, Asp,Met, or Gln; Xaa at position 18 is Asn, His, or Ile; Xaa at position 19is Met or Ile; Xaa at position 21 is Asp or Glu; Xaa at position 23 isIle, Ala, Leu, or Gly; Xaa at position 24 is Ile, Val, or Leu; Xaa atposition 25 is Thr, His, Gln, or Ala; Xaa at position 26 is His or Ala;Xaa at position 29 is Gln, Asn, or Val; Xaa at position 30 is Pro, Gly,or Gln; Xaa at position 31 is Pro, Asp, Gly, or Gln; Xaa at position 32is Leu, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 33 is Pro orGlu; Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Ala, Arg, Gln, Glu,Ile, Phe, Thr or Met; Xaa at position 35 is Leu, Ala, Asn, Pro, Gln, orVal; Xaa at position 37 is Phe, Ser, Pro, or Trp; Xaa at position 38 isAsn or Ala; Xaa at position 42 is Gly, Asp, Ser, Cys, Ala, Asn, Ile,Leu, Met, Tyr or Arg; Xaa at position 44 is Asp or Glu; Xaa at position45 is Gln, Val, Met, Leu, Thr, Ala, Asn, Glu, Ser or Lys; Xaa atposition 46 is Asp, Phe, Ser, Thr, Ala, Asn, Gln, Glu, His, Ile, Lys,Tyr, Val or Cys; Xaa at position 50 is Glu, Ala, Asn, Ser or Asp; Xaa atposition 51 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 54is Arg or Ala; Xaa at position 55 is Arg, Thr, Val, Leu, or Gly; Xaa atposition 56 is Pro, Gly, Ser, Gln, Ala, Arg, Asn, Glu, Leu, Thr, Val orLys; Xaa at position 60 is Ala or Ser; Xaa at position 62 is Asn, Pro,Thr, or Ile; Xaa at position 63 is Arg or Lys; Xaa at position 64 is Alaor Asn; Xaa at position 65 is Val or Thr; Xaa at position 66 is Lys orArg; Xaa at position 67 is Ser, Phe, or His; Xaa at position 68 is Leu,Ile, Phe, or His; Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, orGly; Xaa at position 71 is Ala, Pro, or Arg; Xaa at position 72 is Ser,Glu, Arg, or Asp; Xaa at position 73 is Ala or Leu; Xaa at position 76is Ser, Val, Ala, Asn, Glu, Pro, or Gly; Xaa at position 77 is Ile orLeu; Xaa at position 79 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp;Xaa at position 80 is Asn, Gly, Glu, or Arg; Xaa at position 82 is Leu,Gln, Trp, Arg, Asp, Ala, Asn, Glu, His, Ile, Met, Phe, Ser, Thr, Tyr orVal; Xaa at position 83 is Pro or Thr; Xaa at position 85 is Leu or Val;Xaa at position 87 is Leu or Ser; Xaa at position 88 is Ala or Trp; Xaaat position 91 is Ala or Pro; Xaa at position 93 is Thr, Asp, Ser, Pro,Ala, Leu, or Arg; Xaa at position 95 is His, Pro, Arg, Val, Leu, Gly,Asn, Phe, Ser or Thr; Xaa at position 96 is Pro or Tyr; Xaa at position97 is Ile or Val; Xaa at position 98 is His, Ile, Asn, Leu, Ala, Thr,Arg, Gln, Lys, Met, Ser, Tyr, Val or Pro; Xaa at position 99 is Ile,Leu, or Val; Xaa at position 100 is Lys, Arg, Ile, Gln, Pro, or Ser; Xaaat position 101 is Asp; Xaa at position 104 is Trp or Leu; Xaa atposition 105 is Asn, Pro, Ala, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp,or His; Xaa at position 106 is Glu or Gly; Xaa at position 108 is Arg,Ala, or Ser; Xaa at position 109 is Arg, Thr, Glu, Leu, or Ser; Xaa atposition 112 is Thr, Val, or Gln; Xaa at position 114 is Tyr or Trp; Xaaat position 115 is Leu or Ala; Xaa at position 116 is Lys; Xaa atposition 117 is Thr or Ser; Xaa at position 120 is Asn, Pro, Leu, His,Val, or Gln; Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Asp, orGly; Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile,Tyr, or Cys; Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr,or Leu;wherein from one to three of the amino acids designated by Xaaare different from the corresponding amino acids of native (1-133) humaninterleukin-3; and wherein from 1 to 14 amino acids are optionallydeleted from the N-terminus and/or from 1 to 15 amino acids areoptionally deleted from the C-terminus; and said mutant humaninterleukin-3 polypeptide has at least three times greater cellproliferative activity than native human interleukin-3 in at least oneassay selected from the group consisting of: AML cell proliferation,TF-1 cell proliferation and Methylcellulose assay; and (b) a polypeptidecomprising an N-terminal methionine residue, alanine residue ormethionine-alanine di-peptide immediately preceding said sequenceaccording to (a).
 37. The method according to claim 36, wherein saidmutant human interleukin-3 polypeptide has at least ten times greatercell proliferative activity than native human interleukin-3.
 38. Amethod of treating a side effect of cancer chemotherapy or radiationtherapy in a patient comprising administering to said patient, atherapeutically effective amount of a mutant human interleukin-3 (hIL-3)polypeptide comprising a modified hIL-3 amino acid sequence selectedfrom the group consisting of:(a) a sequence of (SEQ ID NO:19)wherein;Xaa at position 3 is Ser, Lys, Gly, Asp, Met, Gln, or Arg; Xaa atposition 4 is Asn, His, Leu, Ile, Phe, Arg, or Gln; Xaa at position 5 isMet, Phe, Ile, Arg, Gly, Ala, or Cys; Xaa at position 6 is Ile, Cys,Gln, Glu, Arg, Pro, or Ala; Xaa at position 7 is Asp, Phe, Lys, Arg,Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val; Xaa at position 8 is Glu, Trp,Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val, or Gly; Xaa at position 9is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg; Xaa at position10 is Ile, Gly, Val, Arg, Ser, Phe, or Leu; Xaa at position 11 is Thr,His, Gly, Gln, Arg, Pro, or Ala; Xaa at position 12 is His, Thr, Phe,Gly, Arg, Ala, or Trp; Xaa at position 13 is Leu, Gly, Arg, Thr, Ser, orAla; Xaa at position 14 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp; Xaaat position 15 is Gln, Asn, Leu, Pro, Arg, or Val; Xaa at position 16 isPro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys; Xaa at position 17 isPro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa at position 18 is Leu, Val,Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 19 is Pro, Leu, Gln,Ala, Thr, or Glu; Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Glu,Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaa at position 21 is Leu, Ala,Gly, Asn, Pro, Gln, or Val; Xaa at position 22 is Asp, Leu, or Val; Xaaat position 23 is Phe, Ser, Pro, Trp, or Ile; Xaa at position 24 is Asn,or Ala; Xaa at position 26 is Leu, Trp, or Arg; Xaa at position 27 isAsn, Cys, Arg, Leu, His, Met, Pro; Xaa at position 28 is Gly, Asp, Ser,Cys, Ala, Lys, Asn, Thr, Leu, Val, Glu, Phe, Tyr, Ile or Met; Xaa atposition 29 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr,Gly or Ser; Xaa at position 30 is Asp, Ser, Leu, Arg, Lys, Thr, Met,Trp, Glu, Asn, Gln, Ala or Pro; Xaa at position 31 is Gln, Pro, Phe,Val, Met, Leu, Thr, Lys, Asp, Asn, Arg, Ser, Ala, Ile, Glu, His or Trp;Xaa at position 32 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His,Ala, Tyr, Ile, Val or Gly; Xaa at position 33 is Ile, Gly, Val, Ser,Arg, Pro, or His; Xaa at position 34 is Leu, Ser, Cys, Arg, Ile, His,Phe, Glu, Lys, Thr, Ala, Met, Val or Asn; Xaa at position 35 is Met,Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa at position 36 is Glu, Leu,Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln; Xaaat position 37 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position38 is Asn, His, Arg, Leu, Gly, Ser, or Thr; Xaa at position 39 is Leu,Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met; Xaa at position 40 is Arg,Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu; Xaa at position41 is Arg, Thr, Val, Ser, Leu, or Gly; Xaa at position 42 is Pro, Gly,Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys; Xaaat position 43 is Asn or Gly; Xaa at position 44 is Leu, Ser, Asp, Arg,Gln, Val, or Cys; Xaa at position 45 is Glu, Tyr, His, Leu, Pro, or Arg;Xaa at position 46 is Ala, Ser, Pro, Tyr, Asn, or Thr; Xaa at position47 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser; Xaa at position 48 is Asn,His, Val, Arg, Pro, Thr, Asp, or Ile; Xaa at position 49 is Arg, Tyr,Trp, Lys, Ser, His, Pro, or Val; Xaa at position 50 is Ala, Asn, Pro,Ser, or Lys; Xaa at position 51 is Val, Thr, Pro, His, Leu, Phe, or Ser;Xaa at position 52 is Lys, Ile, Arg, Val, Asn, Glu, or Ser; Xaa atposition 53 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His; Xaa atposition 54 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His; Xaa atposition 55 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu; Xaa atposition 56 is Asn, Leu, Val, Trp, Pro, or Ala; Xaa at position 57 isAla, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn; Xaa at position 58is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp; Xaa at position 59 is Ala,Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa at position 60 is Ile, Met,Thr, Pro, Arg, Gly, Ala; Xaa at position 61 is Glu, Lys, Gly, Asp, Pro,Trp, Arg, Ser, Gln, or Leu; Xaa at position 62 is Ser, Val, Ala, Asn,Trp, Glu, Pro, Gly, or Asp; Xaa at position 63 is Ile, Ser, Arg, Thr, orLeu; Xaa at position 64 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg; Xaa atposition 65 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp; Xaa atposition 66 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg; Xaa atposition 67 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys; Xaa atposition 68 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser,Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 69 is Pro, Ala, Thr,Trp, Arg, or Met; Xaa at position 70 is Cys, Glu, Gly, Arg, Met, or Val;Xaa at position 71 is Leu, Asn, Val, or Gln; Xaa at position 72 is Pro,Cys, Arg, Ala, or Lys; Xaa at position 73 is Leu, Ser, Trp, or Gly; Xaaat position 74 is Ala, Lys, Arg, Val, or Trp; Xaa at position 75 is Thr,Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 76 is Ala,Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 77 is Ala, Pro,Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 78 is Pro, Phe, Arg,Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 79 is Thr, Asp,Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 80 is Arg, Ile, Ser,Glu, Leu, Val, Gln, Lys, His, Ala or Pro; Xaa at position 81 is His,Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile orTyr; Xaa at position 82 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaa atposition 83 is Ile, Val, Lys, Ala, or Asn; Xaa at position 84 is His,Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg,Tyr or Pro; Xaa at position 85 is Ile, Leu, Arg, Asp, Val, Pro, Gln,Gly, Ser, Phe, or His; Xaa at position 86 is Lys, Tyr, Leu, His, Arg,Ile, Ser, Gln, or Pro; Xaa at position 87 is Asp; Xaa at position 88 isGly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 89 is Asp, or Ser;Xaa at position 90 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys,Ala, Phe, or Gly; Xaa at position 91 is Asn, Pro, Ala, Phe, Ser, Trp,Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 92 is Glu, Ser,Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 94 is Arg, Lys, Asp,Leu, Thr, Ile, Gln, His, Ser, Ala, or Pro; Xaa at position 95 is Arg,Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 96 is Lys, Asn,Thr, Leu, Gln, Arg, His, Glu, Ser, Ala or Trp; Xaa at position 97 isLeu, Ile, Arg, Asp, or Met; Xaa at position 98 is Thr, Val, Gln, Tyr,Glu, His, Ser, or Phe; Xaa at position 99 is Phe, Ser, Cys, His, Gly,Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position 100 is Tyr,Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 101 is Leu, Asn, Val,Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 102 is Lys; Xaa atposition 103 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa at position104 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa at position 105 isGlu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa at position 106 is Asn,Ala, Pro, Leu, His, Val, or Gln; Xaa at position 107 is Ala, Ser, Ile,Asn, Pro, Lys, Asp, or Gly; Xaa at position 108 is Gln, Ser, Met, Trp,Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa at position 109 is Ala, Met,Glu, His, Ser, Pro, Tyr, or Leu;wherein from one to three of the aminoacids designated by Xaa are different from the corresponding nativeamino acids of (1-133) human interleukin-3; and said mutant humaninterleukin-3 polypeptide has at least three times greater cellproliferative activity than native human interleukin-3 in at least oneassay selected from the group consisting of: AML cell proliferation,TF-1 cell proliferation and Methylcellulose assay; and (b) a polypeptidecomprising an N-terminal methionine residue, alanine residue ormethionine-alanine di-peptide immediately preceding said sequenceaccording to (a).
 39. The method according to claim 38, wherein saidmutant human interleukin-3 polypeptide has at least ten times greatercell proliferative activity than native human interleukin-3.
 40. Themethod according to claim 38, wherein said mutant human interleukin-3polypeptide is selected from the group consisting of:(a) a polypeptidehaving an amino acid sequence of(i) (residues 3-113 of SEQ ID NO:66);(ii) (residues 3-113 of SEQ ID NO:67); (iii) (residues 3-113 of SEQ IDNO:69); or (iv) (SEQ ID NO:218); and (b) an N-terminal methionineresidue, alanine residue or methionine-alanine di-peptide immediatelypreceding said sequence according to (a).
 41. The method according toclaim 40, wherein said mutant human interleukin-3 polypeptide has atleast ten times greater cell proliferative activity than native humaninterleukin-3.
 42. The method according to claim 38, wherein in saidmutant human interleukin-3 (hIL-3) sequence the amino acids which differfrom the corresponding residue in native human interleukin-3 areselected from the group consisting of:position 28 wherein Xaa is Gly,Asp, Ser, Ile, Leu, Met, Tyr, or Ala; position 31 wherein Xaa is Gln,Val, Met or Asn; position 32 wherein Xaa is Asp, Ser, Ala, Gln, His orVal; position 36 wherein Xaa is Glu or Asp; position 37 wherein Xaa isAsn, Pro or Thr; position 48 wherein Xaa is Asn or Pro; position 62wherein Xaa is Ser, or Pro; position 68 wherein Xaa is Leu, Trp, Asp,Asn, Glu, His, Phe, Ser or Tyr; position 81 wherein Xaa is His, Arg,Thr, Asn or Ser; position 84 wherein Xaa is His, Ile, Leu, Ala, Arg,Gln, Lys, Met, Ser, Tyr or Val; position 86 wherein Xaa is Lys or Arg;position 87 wherein Xaa is Asp; position 91 wherein Xaa is Asn, or Pro;position 94 wherein Xaa is Arg, Ala, or Ser; position 102 wherein Xaa isLys; position 107 wherein Xaa is Ala, or Ile; position 108 wherein Xaais Gln, or Ile; position 109 wherein Xaa is Ala, Met or Glu.
 43. Themethod according to claim 42, wherein said mutant human interleukin-3polypeptide has at least ten times greater cell proliferative activitythan native human interleukin-3.
 44. A method of treating a side effectof cancer chemotherapy or radiation therapy in a patient comprisingadministering to said patient, a therapeutically effective amount of amutant human interleukin-3 (hIL-3) polypeptide comprising a modifiedhIL-3 amino acid sequence selected from the group consisting of:(a) asequence of (SEQ ID NO:21)wherein; Xaa at position 3 is Ser, Gly, Asp,Met, or Gln; Xaa at position 4 is Asn, His, or Ile; Xaa at position 5 isMet or Ile; Xaa at position 7 is Asp or Glu; Xaa at position 9 is Ile,Ala, Leu, or Gly; Xaa at position 10 is Ile, Val, or Leu; Xaa atposition 11 is Thr, His, Gln, or Ala; Xaa at position 12 is His or Ala;Xaa at position 15 is Gln, Asn, or Val; Xaa at position 16 is Pro, Gly,or Gln; Xaa at position 17 is Pro, Asp, Gly, or Gln; Xaa at position 18is Leu, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 19 is Pro orGlu; Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Ala, Arg, Gln, Glu,Ile, Phe, Thr or Met; Xaa at position 21 is Leu, Ala, Asn, Pro, Gln, orVal; Xaa at position 23 is Phe, Ser, Pro, or Trp; Xaa at position 24 isAsn or Ala; Xaa at position 28 is Gly, Asp, Ser, Cys, Ala, Asn, Ile,Leu, Met Tyr or Arg; Xaa at position 30 is Asp or Glu; Xaa at position31 is Gln, Val, Met, Leu, Thr, Ala, Asn, Glu, Ser or Lys; Xaa atposition 32 is Asp, Phe, Ser, Thr, Ala, Asn, Gln, Glu, His, Ile, Lys,Tyr, Val or Cys; Xaa at position 36 is Glu, Ala, Asn, Ser or Asp; Xaa atposition 37 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 40is Arg or Ala; Xaa at position 41 is Arg, Thr, Val, Leu, or Gly; Xaa atposition 42 is Pro, Gly, Ser, Gln, Ala, Arg, Asn, Glu, Leu, Thr, Val orLys; Xaa at position 46 is Ala or Ser; Xaa at position 48 is Asn, Pro,Thr, or Ile; Xaa at position 49 is Arg or Lys; Xaa at position 50 is Alaor Asn; Xaa at position 51 is Val or Thr; Xaa at position 52 is Lys orArg; Xaa at position 53 is Ser, Phe, or His; Xaa at position 54 is Leu,Ile, Phe, or His; Xaa at position 55 is Gln, Ala, Pro, Thr, Glu, Arg, orGly; Xaa at position 57 is Ala, Pro, or Arg; Xaa at position 58 is Ser,Glu, Arg, or Asp; Xaa at position 59 is Ala or Leu; Xaa at position 62is Ser, Val, Ala, Asn, Glu, Pro, or Gly; Xaa at position 63 is Ile orLeu; Xaa at position 65 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp;Xaa at position 66 is Asn, Gly, Glu, or Arg; Xaa at position 68 is Leu,Gln, Trp, Arg, Asp, Ala, Asn, Glu, His, Ile, Met, Phe, Ser, Thr, Tyr orVal; Xaa at position 69 is Pro or Thr; Xaa at position 71 is Leu or Val;Xaa at position 73 is Leu or Ser; Xaa at position 74 is Ala or Trp; Xaaat position 77 is Ala or Pro; Xaa at position 79 is Thr, Asp, Ser, Pro,Ala, Leu, or Arg; Xaa at position 81 is His, Pro, Arg, Val, Leu, Gly,Asn, Phe, Ser or Thr; Xaa at position 82 is Pro or Tyr; Xaa at position83 is Ile or Val; Xaa at position 84 is His, Ile, Asn, Leu, Ala, Thr,Arg, Gln, Lys, Met, Ser, Tyr, Val or Pro; Xaa at position 85 is Ile,Leu, or Val; Xaa at position 86 is Lys, Arg, Ile, Gln, Pro, or Ser; Xaaat position 87 is Asp; Xaa at position 90 is Trp or Leu; Xaa at position91 is Asn, Pro, Ala, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaaat position 92 is Glu, or Gly; Xaa at position 94 is Arg, Ala, or Ser;Xaa at position 95 is Arg, Thr, Glu, Leu, or Ser; Xaa at position 98 isThr, Val, or Gln; Xaa at position 100 is Tyr or Trp; Xaa at position 101is Leu or Ala; Xaa at position 102 is Lys; Xaa at position 103 is Thr orSer; Xaa at position 106 is Asn, Pro, Leu, His, Val, or Gln; Xaa atposition 107 is Ala, Ser, Ile, Asn, Pro, Asp, or Gly; Xaa at position108 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa atposition 109 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;wherein fromone to three of the amino acids designated by Xaa are different from thecorresponding amino acids of native (1-133) human interleukin-3; andsaid mutant human interleukin-3 polypeptide has at least three timesgreater cell proliferative activity than native human interleukin-3 inat least one assay selected from the group consisting of: AML cellproliferation, TF-1 cell proliferation and Methylcellulose assay; and(b) a polypeptide comprising an N-terminal methionine residue, alanineresidue or methionine-alanine di-peptide immediately preceding saidsequence according to (a).
 45. The method according to claim 44, whereinsaid mutant human interleukin-3 polypeptide has at least ten timesgreater cell proliferative activity than native human interleukin-3. 46.A method of treating a patient having an immunodeficiency orhematopoietic disorder consisting of administering to said patient, atherapeutically effective amount of a mutant human interleukin-3 (hIL-3)polypeptide consisting of a modified hIL-3 amino acid sequence selectedfrom the group consisting of:(a) a sequence of (SEQ ID NO:15)wherein;Xaa at position 17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg; Xaa atposition 18 is Asn, His, Leu, Ile, Phe, Arg, or Gln; Xaa at position 19is Met, Phe, Ile, Arg, Gly, Ala, or Cys; Xaa at position 20 is Ile, Cys,Gln, Glu, Arg, Pro, or Ala; Xaa at position 21 is Asp, Phe, Lys, Arg,Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val; Xaa at position 22 is Glu,Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val or Gly; Xaa at position23 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg; Xaa atposition 24 is Ile, Gly, Val, Arg, Ser, Phe, or Leu; Xaa at position 25is Thr, His, Gly, Gln, Arg, Pro, or Ala; Xaa at position 26 is His, Thr,Phe, Gly, Arg, Ala, or Trp; Xaa at position 27 is Leu, Gly, Arg, Thr,Ser, or Ala; Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val orTrp; Xaa at position 29 is Gln, Asn, Leu, Pro, Arg, or Val; Xaa atposition 30 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys; Xaa atposition 31 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa at position 32is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 33 is Pro,Leu, Gln, Ala, Thr, or Glu; Xaa at position 34 is Leu, Val, Gly, Ser,Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaa at position 35 isLeu, Ala, Gly, Asn, Pro, Gln, or Val; Xaa at position 36 is Asp, Leu, orVal; Xaa at position 37 is Phe, Ser, Pro, Trp, or Ile; Xaa at position38 is Asn, or Ala; Xaa at position 40 is Leu, Trp, or Arg; Xaa atposition 41 is Asn, Cys, Arg, Leu, His, Met, or Pro; Xaa at position 42is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Metor Ala; Xaa at position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys,Gln, Arg, Thr, Gly or Ser; Xaa at position 44 is Asp, Ser, Leu, Arg,Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro; Xaa at position 45 isGln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala,Ile, Glu or His; Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu,Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaa at position 47 isIle, Gly, Val, Ser, Arg, Pro, or His; Xaa at position 48 is Leu, Ser,Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val or Asn; Xaa atposition 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa atposition 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val,His, Phe, Met or Gln; Xaa at position 51 is Asn, Arg, Met, Pro, Ser,Thr, or His; Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, or Thr;Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met;Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His,Ala or Leu; Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly; Xaaat position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr,Phe, Leu, Val or Lys; Xaa at position 57 is Asn or Gly; Xaa at position58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys; Xaa at position 59 is Glu,Tyr, His, Leu, Pro, or Arg; Xaa at position 60 is Ala, Ser, Pro, Tyr,Asn, or Thr; Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser;Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile; Xaa atposition 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val; Xaa atposition 64 is Ala, Asn, Pro, Ser, or Lys; Xaa at position 65 is Val,Thr, Pro, His, Leu, Phe, or Ser; Xaa at position 66 is Lys, Ile, Arg,Val, Asn, Glu, or Ser; Xaa at position 67 is Ser, Ala, Phe, Val, Gly,Asn, Ile, Pro, or His; Xaa at position 68 is Leu, Val, Trp, Ser, Ile,Phe, Thr, or His; Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg,Trp, Gly, or Leu; Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, orAsn; Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa atposition 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala; Xaa at position 75 isGlu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu; Xaa at position 76is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp; Xaa at position 77 isIle, Ser, Arg, Thr, or Leu; Xaa at position 78 is Leu, Ala, Ser, Glu,Phe, Gly, or Arg; Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile,Gly, or Asp; Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, orArg; Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr,Ser, Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 83 is Pro, Ala,Thr, Trp, Arg, or Met; Xaa at position 84 is Cys, Glu, Gly, Arg, Met, orVal; Xaa at position 85 is Leu, Asn, Val, or Gln; Xaa at position 86 isPro, Cys, Arg, Ala, or Lys; Xaa at position 87 is Leu, Ser, Trp, or Gly;Xaa at position 88 is Ala, Lys, Arg, Val, or Trp; Xaa at position 89 isThr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 90 isAla, Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 91 is Ala,Pro, Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 92 is Pro, Phe,Arg, Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 93 is Thr,Asp, Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 94 is Arg, Ile,Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro; Xaa at position 95 isHis, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe,Ile, or Tyr; Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaaat position 97 is Ile, Val, Lys, Ala, or Asn; Xaa at position 98 is His,Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg,Tyr or Pro; Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln,Gly, Ser, Phe, or His; Xaa at position 100 is Lys, Tyr, Leu, His, Arg,Ile, Ser, Gln, or Pro; Xaa at position 101 is Asp; Xaa at position 102is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 103 is Asp, orSer; Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln,Lys, Ala, Phe, or Gly; Xaa at position 105 is Asn, Pro, Ala, Phe, Ser,Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 106 is Glu,Ser, Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 108 is Arg, Lys,Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro; Xaa at position 109 isArg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 110 is Lys,Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, Ala, or Trp; Xaa atposition 111 is Leu, Ile, Arg, Asp, or Met; Xaa at position 112 is Thr,Val, Gln, Tyr, Glu, His, Ser, or Phe; Xaa at position 113 is Phe, Ser,Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 115 is Leu,Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 116 isLys; Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa atposition 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa atposition 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa atposition 120 is Asn, Ala, Pro, Leu, His, Val, or Gln; Xaa at position121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly; Xaa at position 122 isGln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa atposition 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;wherein fromone to three of the amino acids designated by Xaa are different from thecorresponding amino acids of native (1-133) human interleukin-3; andwherein from 1 to 14 amino acids are optionally deleted from theN-terminus and/or from 1 to 15 amino acids are optionally deleted fromthe C-terminus; and said mutant human interleukin-3 polypeptide has atleast three times greater cell proliferative activity than native humaninterleukin-3 in at least one assay selected from the group consistingof: AML cell proliferation, TF-1 cell proliferation and Methylcelluloseassay; and (b) a polypeptide consisting of an N-terminal methionineresidue, alanine residue or methionine-alanine di-peptide immediatelypreceding said sequence according to (a).
 47. The method according toclaim 46, wherein said mutant human interleukin-3 polypeptide has atleast ten times greater cell proliferative activity than native humaninterleukin-3.
 48. The method according to claim 46 wherein in saidmutant human interleukin-3 (hIL-3) sequence the amino acids which differfrom the corresponding residue in native human interleukin-3 areselected from the group consisting of:position 42 wherein Xaa is Gly,Asp, Ser, Ile, Leu, Met, Tyr, or Ala; position 45 wherein Xaa is Gln,Val, Met or Asn; position 46 wherein Xaa is Asp, Ser, Gln, His or Val;position 50 wherein Xaa is Glu or Asp; position 51 wherein Xaa is Asn,Pro or Thr; position 62 wherein Xaa is Asn or Pro; position 76 whereinXaa is Ser, or Pro; position 82 wherein Xaa is Leu, Trp, Asp, Asn Glu,His, Phe, Ser or Tyr; position 95 wherein Xaa is His, Arg, Thr, Asn orSer; position 98 wherein Xaa is His, Ile, Leu, Ala, Gln, Lys, Met, Ser,Tyr or Val; position 100 wherein Xaa is Lys or Arg; position 101 whereinXaa is Asp; position 105 wherein Xaa is Asn, or Pro; position 108wherein Xaa is Arg, Ala, or Ser; position 116 wherein Xaa is Lys;position 121 wherein Xaa is Ala, or Ile; position 122 wherein Xaa isGln, or Ile; position 123 wherein Xaa is Ala, Met or Glu.
 49. The methodaccording to claim 48, wherein said mutant human interleukin-3polypeptide has at least ten times greater cell proliferative activitythan native human interleukin-3.
 50. A method of treating a patienthaving an immunodeficiency or hematopoietic disorder consisting ofadministering to said patient, a therapeutically effective amount of amutant human interleukin-3 (hIL-3) polypeptide consisting of a modifiedhIL-3 amino acid sequence selected from the group consisting of:(a) asequence of (SEQ ID NO:17)wherein; Xaa at position 17 is Ser, Gly, Asp,Met, or Gln; Xaa at position 18 is Asn, His, or Ile; Xaa at position 19is Met or Ile; Xaa at position 21 is Asp or Glu; Xaa at position 23 isIle, Ala, Leu, or Gly; Xaa at position 24 is Ile, Val, or Leu; Xaa atposition 25 is Thr, His, Gln, or Ala; Xaa at position 26 is His or Ala;Xaa at position 29 is Gln, Asn, or Val; Xaa at position 30 is Pro, Gly,or Gln; Xaa at position 31 is Pro, Asp, Gly, or Gln; Xaa at position 32is Leu, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 33 is Pro orGlu; Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Ala, Arg, Gln, Glu,Ile, Phe, Thr or Met; Xaa at position 35 is Leu, Ala, Asn, Pro, Gln, orVal; Xaa at position 37 is Phe, Ser, Pro, or Trp; Xaa at position 38 isAsn or Ala; Xaa at position 42 is Gly, Asp, Ser, Cys, Ala, Asn, Ile,Leu, Met, Tyr or Arg; Xaa at position 44 is Asp or Glu; Xaa at position45 is Gln, Val, Met, Leu, Thr, Ala, Asn, Glu, Ser or Lys; Xaa atposition 46 is Asp, Phe, Ser, Thr, Ala, Asn, Gln, Glu, His, Ile, Lys,Tyr, Val or Cys; Xaa at position 50 is Glu, Ala, Asn, Ser or Asp; Xaa atposition 51 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 54is Arg or Ala; Xaa at position 55 is Arg, Thr, Val, Leu, or Gly; Xaa atposition 56 is Pro, Gly, Ser, Gln, Ala, Arg, Asn, Glu, Leu, Thr, Val orLys; Xaa at position 60 is Ala or Ser; Xaa at position 62 is Asn, Pro,Thr, or Ile; Xaa at position 63 is Arg or Lys; Xaa at position 64 is Alaor Asn; Xaa at position 65 is Val or Thr; Xaa at position 66 is Lys orArg; Xaa at position 67 is Ser, Phe, or His; Xaa at position 68 is Leu,Ile, Phe, or His; Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, orGly; Xaa at position 71 is Ala, Pro, or Arg; Xaa at position 72 is Ser,Glu, Arg, or Asp; Xaa at position 73 is Ala or Leu; Xaa at position 76is Ser, Val, Ala, Asn, Glu, Pro, or Gly; Xaa at position 77 is Ile orLeu; Xaa at position 79 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp;Xaa at position 80 is Asn, Gly, Glu, or Arg; Xaa at position 82 is Leu,Gln, Trp, Arg, Asp, Ala, Asn, Glu, His, Ile, Met, Phe, Ser, Thr, Tyr orVal; Xaa at position 83 is Pro or Thr; Xaa at position 85 is Leu or Val;Xaa at position 87 is Leu or Ser; Xaa at position 88 is Ala or Trp; Xaaat position 91 is Ala or Pro; Xaa at position 93 is Thr, Asp, Ser, Pro,Ala, Leu, or Arg; Xaa at position 95 is His, Pro, Arg, Val, Leu, Gly,Asn, Phe, Ser or Thr; Xaa at position 96 is Pro or Tyr; Xaa at position97 is Ile or Val; Xaa at position 98 is His, Ile, Asn, Leu, Ala, Thr,Arg, Gln, Lys, Met, Ser, Tyr, Val or Pro; Xaa at position 99 is Ile,Leu, or Val; Xaa at position 100 is Lys, Arg, Ile, Gln, Pro, or Ser; Xaaat position 101 is Asp; Xaa at position 104 is Trp or Leu; Xaa atposition 105 is Asn, Pro, Ala, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp,or His; Xaa at position 106 is Glu or Gly; Xaa at position 108 is Arg,Ala, or Ser; Xaa at position 109 is Arg, Thr, Glu, Leu, or Ser; Xaa atposition 112 is Thr, Val, or Gln; Xaa at position 114 is Tyr or Trp; Xaaat position 115 is Leu or Ala; Xaa at position 116 is Lys; Xaa atposition 117 is Thr or Ser; Xaa at position 120 is Asn, Pro, Leu, His,Val, or Gln; Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Asp, orGly; Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile,Tyr, or Cys; Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr,or Leu;wherein from one to three of the amino acids designated by Xaaare different from the corresponding amino acids of native (1-133) humaninterleukin-3; and wherein from 1 to 14 amino acids are optionallydeleted from the N-terminus and/or from 1 to 15 amino acids areoptionally deleted from the C-terminus; and said mutant humaninterleukin-3 polypeptide has at least three times greater cellproliferative activity than native human interleukin-3 in at least oneassay selected from the group consisting of: AML cell proliferation,TF-1 cell proliferation and Methylcellulose assay; and (b) a polypeptideconsisting of an N-terminal methionine residue, alanine residue ormethionine-alanine di-peptide immediately preceding said sequenceaccording to (a).
 51. The method according to claim 50, wherein saidmutant human interleukin-3 polypeptide has at least ten times greatercell proliferative activity than native human interleukin-3.
 52. Amethod of treating a patient having an immunodeficiency or hematopoieticdisorder consisting of administering to said patient, a therapeuticallyeffective amount of a mutant human interleukin-3 (hIL-3) polypeptideconsisting of a modified hIL-3 amino acid sequence selected from thegroup consisting of:(a) a sequence of (SEQ ID NO:19)wherein; Xaa atposition 3 is Ser, Lys, Gly, Asp, Met, Gln, or Arg; Xaa at position 4 isAsn, His, Leu, Ile, Phe, Arg, or Gln; Xaa at position 5 is Met, Phe,Ile, Arg, Gly, Ala, or Cys; Xaa at position 6 is Ile, Cys, Gln, Glu,Arg, Pro, or Ala; Xaa at position 7 is Asp, Phe, Lys, Arg, Ala, Gly,Glu, Gln, Asn, Thr, Ser or Val; Xaa at position 8 is Glu, Trp, Pro, Ser,Ala, His, Asp, Asn, Gln, Leu, Val, or Gly; Xaa at position 9 is Ile,Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg; Xaa at position 10 isIle, Gly, Val, Arg, Ser, Phe, or Leu; Xaa at position 11 is Thr, His,Gly, Gln, Arg, Pro, or Ala; Xaa at position 12 is His, Thr, Phe, Gly,Arg, Ala, or Trp; Xaa at position 13 is Leu, Gly, Arg, Thr, Ser, or Ala;Xaa at position 14 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp; Xaa atposition 15 is Gln, Asn, Leu, Pro, Arg, or Val; Xaa at position 16 isPro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys; Xaa at position 17 isPro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa at position 18 is Leu, Val,Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 19 is Pro, Leu, Gln,Ala, Thr, or Glu; Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Glu,Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaa at position 21 is Leu, Ala,Gly, Asn, Pro, Gln, or Val; Xaa at position 22 is Asp, Leu, or Val; Xaaat position 23 is Phe, Ser, Pro, Trp, or Ile; Xaa at position 24 is Asn,or Ala; Xaa at position 26 is Leu, Trp, or Arg; Xaa at position 27 isAsn, Cys, Arg, Leu, His, Met, Pro; Xaa at position 28 is Gly, Asp, Ser,Cys, Ala, Lys, Asn, Thr, Leu, Val, Glu, Phe, Tyr, Ile or Met; Xaa atposition 29 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr,Gly or Ser; Xaa at position 30 is Asp, Ser, Leu, Arg, Lys, Thr, Met,Trp, Glu, Asn, Gln, Ala or Pro; Xaa at position 31 is Gln, Pro, Phe,Val, Met, Leu, Thr, Lys, Asp, Asn, Arg, Ser, Ala, Ile, Glu, His or Trp;Xaa at position 32 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His,Ala, Tyr, Ile, Val or Gly; Xaa at position 33 is Ile, Gly, Val, Ser,Arg, Pro, or His; Xaa at position 34 is Leu, Ser, Cys, Arg, Ile, His,Phe, Glu, Lys, Thr, Ala, Met, Val or Asn; Xaa at position 35 is Met,Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa at position 36 is Glu, Leu,Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln; Xaaat position 37 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position38 is Asn, His, Arg, Leu, Gly, Ser, or Thr; Xaa at position 39 is Leu,Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met; Xaa at position 40 is Arg,Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu; Xaa at position41 is Arg, Thr, Val, Ser, Leu, or Gly; Xaa at position 42 is Pro, Gly,Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys; Xaaat position 43 is Asn or Gly; Xaa at position 44 is Leu, Ser, Asp, Arg,Gln, Val, or Cys; Xaa at position 45 is Glu, Tyr, His, Leu, Pro, or Arg;Xaa at position 46 is Ala, Ser, Pro, Tyr, Asn, or Thr; Xaa at position47 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser; Xaa at position 48 is Asn,His, Val, Arg, Pro, Thr, Asp, or Ile; Xaa at position 49 is Arg, Tyr,Trp, Lys, Ser, His, Pro, or Val; Xaa at position 50 is Ala, Asn, Pro,Ser, or Lys; Xaa at position 51 is Val, Thr, Pro, His, Leu, Phe, or Ser;Xaa at position 52 is Lys, Ile, Arg, Val, Asn, Glu, or Ser; Xaa atposition 53 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His; Xaa atposition 54 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His; Xaa atposition 55 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu; Xaa atposition 56 is Asn, Leu, Val, Trp, Pro, or Ala; Xaa at position 57 isAla, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn; Xaa at position 58is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp; Xaa at position 59 is Ala,Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa at position 60 is Ile, Met,Thr, Pro, Arg, Gly, Ala; Xaa at position 61 is Glu, Lys, Gly, Asp, Pro,Trp, Arg, Ser, Gln, or Leu; Xaa at position 62 is Ser, Val, Ala, Asn,Trp, Glu, Pro, Gly, or Asp; Xaa at position 63 is Ile, Ser, Arg, Thr, orLeu; Xaa at position 64 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg; Xaa atposition 65 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp; Xaa atposition 66 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg; Xaa atposition 67 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys; Xaa atposition 68 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser,Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 69 is Pro, Ala, Thr,Trp, Arg, or Met; Xaa at position 70 is Cys, Glu, Gly, Arg, Met, or Val;Xaa at position 71 is Leu, Asn, Val, or Gln; Xaa at position 72 is Pro,Cys, Arg, Ala, or Lys; Xaa at position 73 is Leu, Ser, Trp, or Gly; Xaaat position 74 is Ala, Lys, Arg, Val, or Trp; Xaa at position 75 is Thr,Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 76 is Ala,Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 77 is Ala, Pro,Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 78 is Pro, Phe, Arg,Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 79 is Thr, Asp,Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 80 is Arg, Ile, Ser,Glu, Leu, Val, Gln, Lys, His, Ala or Pro; Xaa at position 81 is His,Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile orTyr; Xaa at position 82 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaa atposition 83 is Ile, Val, Lys, Ala, or Asn; Xaa at position 84 is His,Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg,Tyr or Pro; Xaa at position 85 is Ile, Leu, Arg, Asp, Val, Pro, Gln,Gly, Ser, Phe, or His; Xaa at position 86 is Lys, Tyr, Leu, His, Arg,Ile, Ser, Gln, or Pro; Xaa at position 87 is Asp; Xaa at position 88 isGly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 89 is Asp, or Ser;Xaa at position 90 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys,Ala, Phe, or Gly; Xaa at position 91 is Asn, Pro, Ala, Phe, Ser, Trp,Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 92 is Glu, Ser,Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 94 is Arg, Lys, Asp,Leu, Thr, Ile, Gln, His, Ser, Ala, or Pro; Xaa at position 95 is Arg,Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 96 is Lys, Asn,Thr, Leu, Gln, Arg, His, Glu, Ser, Ala or Trp; Xaa at position 97 isLeu, Ile, Arg, Asp, or Met; Xaa at position 98 is Thr, Val, Gln, Tyr,Glu, His, Ser, or Phe; Xaa at position 99 is Phe, Ser, Cys, His, Gly,Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position 100 is Tyr,Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 101 is Leu, Asn, Val,Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 102 is Lys; Xaa atposition 103 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa at position104 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa at position 105 isGlu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa at position 106 is Asn,Ala, Pro, Leu, His, Val, or Gln; Xaa at position 107 is Ala, Ser, Ile,Asn, Pro, Lys, Asp, or Gly; Xaa at position 108 is Gln, Ser, Met, Trp,Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa at position 109 is Ala, Met,Glu, His, Ser, Pro, Tyr, or Leu;wherein from one to three of the aminoacids designated by Xaa are different from the corresponding nativeamino acids of (1-133) human interleukin-3; and said mutant humaninterleukin-3 polypeptide has at least three times greater cellproliferative activity than native human interleukin-3 in at least oneassay selected from the group consisting of: AML cell proliferation,TF-1 cell proliferation and Methylcellulose assay; and (b) a polypeptideconsisting of an N-terminal methionine residue, alanine residue ormethionine-alanine di-peptide immediately preceding said sequenceaccording to (a).
 53. The method according to claim 52, wherein saidmutant human interleukin-3 polypeptide has at least ten times greatercell proliferative activity than native human interleukin-3.
 54. Themethod according to claim 52, wherein said mutant human interleukin-3polypeptide is selected from the group consisting of:(a) a polypeptidehaving an amino acid sequence of(i) (residues 3-113 of SEQ ID NO:66);(ii) (residues 3-113 of SEQ ID NO:67); (iii) (residues 3-113 of SEQ IDNO:69); or (iv) (SEQ ID NO:218); and (b) an N-terminal methionineresidue, alanine residue or methionine-alanine di-peptide immediatelypreceding said sequence according to (a).
 55. The method according toclaim 54, wherein said mutant human interleukin-3 polypeptide has atleast ten times greater cell proliferative activity than native humaninterleukin-3.
 56. The method according to claim 52, wherein in saidmutant human interleukin-3 (hIL-3) sequence the amino acids which differfrom the corresponding residue in native human interleukin-3 areselected from the group consisting of:position 28 wherein Xaa is Gly,Asp, Ser, Ile, Leu, Met, Tyr, or Ala; position 31 wherein Xaa is Gln,Val, Met or Asn; position 32 wherein Xaa is Asp, Ser, Ala, Gln, His orVal; position 36 wherein Xaa is Glu or Asp; position 37 wherein Xaa isAsn, Pro or Thr; position 48 wherein Xaa is Asn or Pro; position 62wherein Xaa is Ser, or Pro; position 68 wherein Xaa is Leu, Trp, Asp,Asn, Glu, His, Phe, Ser or Tyr; position 81 wherein Xaa is His, Arg,Thr, Asn or Ser; position 84 wherein Xaa is His, Ile, Leu, Ala, Arg,Gln, Lys, Met, Ser, Tyr or Val; position 86 wherein Xaa is Lys or Arg;position 87 wherein Xaa is Asp; position 91 wherein Xaa is Asn, or Pro;position 94 wherein Xaa is Arg, Ala, or Ser; position 102 wherein Xaa isLys; position 107 wherein Xaa is Ala, or Ile; position 108 wherein Xaais Gln, or Ile; position 109 wherein Xaa is Ala, Met or Glu.
 57. Themethod according to claim 56, wherein said mutant human interleukin-3polypeptide has at least ten times greater cell proliferative activitythan native human interleukin-3.
 58. A method of treating a patienthaving an immunodeficiency or hematopoietic disorder consisting ofadministering to said patient, a therapeutically effective amount of amutant human interleukin-3 (hIL-3) polypeptide consisting of a modifiedhIL-3 amino acid sequence selected from the group consisting of:(a) asequence of (SEQ ID NO:21)wherein; Xaa at position 3 is Ser, Gly, Asp,Met, or Gln; Xaa at position 4 is Asn, His, or Ile; Xaa at position 5 isMet or Ile; Xaa at position 7 is Asp or Glu; Xaa at position 9 is Ile,Ala, Leu, or Gly; Xaa at position 10 is Ile, Val, or Leu; Xaa atposition 11 is Thr, His, Gln, or Ala; Xaa at position 12 is His or Ala;Xaa at position 15 is Gln, Asn, or Val; Xaa at position 16 is Pro, Gly,or Gln; Xaa at position 17 is Pro, Asp, Gly, or Gln; Xaa at position 18is Leu, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 19 is Pro orGlu; Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Ala, Arg, Gln, Glu,Ile, Phe, Thr or Met; Xaa at position 21 is Leu, Ala, Asn, Pro, Gln, orVal; Xaa at position 23 is Phe, Ser, Pro, or Trp; Xaa at position 24 isAsn or Ala; Xaa at position 28 is Gly, Asp, Ser, Cys, Ala, Asn, Ile,Leu, Met Tyr or Arg; Xaa at position 30 is Asp or Glu; Xaa at position31 is Gln, Val, Met, Leu, Thr, Ala, Asn, Glu, Ser or Lys; Xaa atposition 32 is Asp, Phe, Ser, Thr, Ala, Asn, Gln, Glu, His, Ile, Lys,Tyr, Val or Cys; Xaa at position 36 is Glu, Ala, Asn, Ser or Asp; Xaa atposition 37 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 40is Arg or Ala; Xaa at position 41 is Arg, Thr, Val, Leu, or Gly; Xaa atposition 42 is Pro, Gly, Ser, Gln, Ala, Arg, Asn, Glu, Leu, Thr, Val orLys; Xaa at position 46 is Ala or Ser; Xaa at position 48 is Asn, Pro,Thr, or Ile; Xaa at position 49 is Arg or Lys; Xaa at position 50 is Alaor Asn; Xaa at position 51 is Val or Thr; Xaa at position 52 is Lys orArg; Xaa at position 53 is Ser, Phe, or His; Xaa at position 54 is Leu,Ile, Phe, or His; Xaa at position 55 is Gln, Ala, Pro, Thr, Glu, Arg, orGly; Xaa at position 57 is Ala, Pro, or Arg; Xaa at position 58 is Ser,Glu, Arg, or Asp; Xaa at position 59 is Ala or Leu; Xaa at position 62is Ser, Val, Ala, Asn, Glu, Pro, or Gly; Xaa at position 63 is Ile orLeu; Xaa at position 65 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp;Xaa at position 66 is Asn, Gly, Glu, or Arg; Xaa at position 68 is Leu,Gln, Trp, Arg, Asp, Ala, Asn, Glu, His, Ile, Met, Phe, Ser, Thr, Tyr orVal; Xaa at position 69 is Pro or Thr; Xaa at position 71 is Leu or Val;Xaa at position 73 is Leu or Ser; Xaa at position 74 is Ala or Trp; Xaaat position 77 is Ala or Pro; Xaa at position 79 is Thr, Asp, Ser, Pro,Ala, Leu, or Arg; Xaa at position 81 is His, Pro, Arg, Val, Leu, Gly,Asn, Phe, Ser or Thr; Xaa at position 82 is Pro or Tyr; Xaa at position83 is Ile or Val; Xaa at position 84 is His, Ile, Asn, Leu, Ala, Thr,Arg, Gln, Lys, Met, Ser, Tyr, Val or Pro; Xaa at position 85 is Ile,Leu, or Val; Xaa at position 86 is Lys, Arg, Ile, Gln, Pro, or Ser; Xaaat position 87 is Asp; Xaa at position 90 is Trp or Leu; Xaa at position91 is Asn, Pro, Ala, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaaat position 92 is Glu, or Gly; Xaa at position 94 is Arg, Ala, or Ser;Xaa at position 95 is Arg, Thr, Glu, Leu, or Ser; Xaa at position 98 isThr, Val, or Gln; Xaa at position 100 is Tyr or Trp; Xaa at position 101is Leu or Ala; Xaa at position 102 is Lys; Xaa at position 103 is Thr orSer; Xaa at position 106 is Asn, Pro, Leu, His, Val, or Gln; Xaa atposition 107 is Ala, Ser, Ile, Asn, Pro, Asp, or Gly; Xaa at position108 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa atposition 109 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;wherein fromone to three of the amino acids designated by Xaa are different from thecorresponding amino acids of native (1-133) human interleukin-3; andsaid mutant human interleukin-3 polypeptide has at least three timesgreater cell proliferative activity than native human interleukin-3 inat least one assay selected from the group consisting of: AML cellproliferation, TF-1 cell proliferation and Methylcellulose assay; and(b) a polypeptide consisting of an N-terminal methionine residue,alanine residue or methionine-alanine di-peptide immediately precedingsaid sequence according to (a).
 59. The method according to claim 58,wherein said mutant human interleukin-3 polypeptide has at least tentimes greater cell proliferative activity than native humaninterleukin-3.
 60. The method according to claim 46, 47, 50, 57, 48, 49,52, 53, 54, 55, 58, 59, 56 or 57 wherein said immunodeficiency orhematopoietic disorder is the result of a viral infection, bacterialinfection or fungal infection.
 61. The method according to claim 46, 47,50, 57, 48, 49, 52, 53, 54, 55, 58, 59, 56 or 57 wherein saidimmunodeficiency or hematopoietic disorder is the result of cancerradiation therapy or chemotherapy.
 62. The method according to claim 46,47, 50, 57, 48, 49, 52, 53, 54, 55, 58, 59, 56 or 57 wherein saidimmunodeficiency is the result of the treatment of a patient with a drugwhich causes bone marrow suppression.
 63. A method of treating a patientconsisting of the steps of:(i) administering to said patient, an amountof a mutant human interleukin-3 (IL-3) polypeptide, effective to promotethe proliferation and/or differentiation of hematopoietic cells in saidpatient, wherein said mutant human interleukin-3 (hIL-3) polypeptideconsists of a modified hIL-3 amino acid sequence selected from the groupconsisting of: (a) a sequence of (SEQ ID NO:15)wherein; Xaa at position17 is Ser, Lys, Gly, Asp, Met, Gln, or Arg; Xaa at position 18 is Asn,His, Leu, Ile, Phe, Arg, or Gln; Xaa at position 19 is Met, Phe, Ile,Arg, Gly, Ala, or Cys; Xaa at position 20 is Ile, Cys, Gln, Glu, Arg,Pro, or Ala; Xaa at position 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu,Gln, Asn, Thr, Ser or Val; Xaa at position 22 is Glu, Trp, Pro, Ser,Ala, His, Asp, Asn, Gln, Leu, Val or Gly; Xaa at position 23 is Ile,Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg; Xaa at position 24 isIle, Gly, Val, Arg, Ser, Phe, or Leu; Xaa at position 25 is Thr, His,Gly, Gln, Arg, Pro, or Ala; Xaa at position 26 is His, Thr, Phe, Gly,Arg, Ala, or Trp; Xaa at position 27 is Leu, Gly, Arg, Thr, Ser, or Ala;Xaa at position 28 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp; Xaa atposition 29 is Gln, Asn, Leu, Pro, Arg, or Val; Xaa at position 30 isPro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys; Xaa at position 31 isPro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa at position 32 is Leu, Val,Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 33 is Pro, Leu, Gln,Ala, Thr, or Glu; Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Glu,Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaa at position 35 is Leu, Ala,Gly, Asn, Pro, Gln, or Val; Xaa at position 36 is Asp, Leu, or Val; Xaaat position 37 is Phe, Ser, Pro, Trp, or Ile; Xaa at position 38 is Asn,or Ala; Xaa at position 40 is Leu, Trp, or Arg; Xaa at position 41 isAsn, Cys, Arg, Leu, His, Met, or Pro; Xaa at position 42 is Gly, Asp,Ser, Cys, Asn, Lys, Thr, Leu, Val, Glu, Phe, Tyr, Ile, Met or Ala; Xaaat position 43 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr,Gly or Ser; Xaa at position 44 is Asp, Ser, Leu, Arg, Lys, Thr, Met,Trp, Glu, Asn, Gln, Ala or Pro; Xaa at position 45 is Gln, Pro, Phe,Val, Met, Leu, Thr, Lys, Trp, Asp, Asn, Arg, Ser, Ala, Ile, Glu or His;Xaa at position 46 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His,Ala, Tyr, Ile, Val or Gly; Xaa at position 47 is Ile, Gly, Val, Ser,Arg, Pro, or His; Xaa at position 48 is Leu, Ser, Cys, Arg, Ile, His,Phe, Glu, Lys, Thr, Ala, Met, Val or Asn; Xaa at position 49 is Met,Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa at position 50 is Glu, Leu,Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln; Xaaat position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position52 is Asn, His, Arg, Leu, Gly, Ser, or Thr; Xaa at position 53 is Leu,Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met; Xaa at position 54 is Arg,Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu; Xaa at position55 is Arg, Thr, Val, Ser, Leu, or Gly; Xaa at position 56 is Pro, Gly,Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys; Xaaat position 57 is Asn or Gly; Xaa at position 58 is Leu, Ser, Asp, Arg,Gln, Val, or Cys; Xaa at position 59 is Glu, Tyr, His, Leu, Pro, or Arg;Xaa at position 60 is Ala, Ser, Pro, Tyr, Asn, or Thr; Xaa at position61 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser; Xaa at position 62 is Asn,His, Val, Arg, Pro, Thr, Asp, or Ile; Xaa at position 63 is Arg, Tyr,Trp, Lys, Ser, His, Pro, or Val; Xaa at position 64 is Ala, Asn, Pro,Ser, or Lys; Xaa at position 65 is Val, Thr, Pro, His, Leu, Phe, or Ser;Xaa at position 66 is Lys, Ile, Arg, Val, Asn, Glu, or Ser; Xaa atposition 67 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His; Xaa atposition 68 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His; Xaa atposition 69 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu; Xaa atposition 70 is Asn, Leu, Val, Trp, Pro, or Ala; Xaa at position 71 isAla, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn; Xaa at position 72is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp; Xaa at position 73 is Ala,Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa at position 74 is Ile, Met,Thr, Pro, Arg, Gly, Ala; Xaa at position 75 is Glu, Lys, Gly, Asp, Pro,Trp, Arg, Ser, Gln, or Leu; Xaa at position 76 is Ser, Val, Ala, Asn,Trp, Glu, Pro, Gly, or Asp; Xaa at position 77 is Ile, Ser, Arg, Thr, orLeu; Xaa at position 78 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg; Xaa atposition 79 is Lys, Thr, Asn, Met, Arg, Ile, Gly, or Asp; Xaa atposition 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg; Xaa atposition 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys; Xaa atposition 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser,Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 83 is Pro, Ala, Thr,Trp, Arg, or Met; Xaa at position 84 is Cys, Glu, Gly, Arg, Met, or Val;Xaa at position 85 is Leu, Asn, Val, or Gln; Xaa at position 86 is Pro,Cys, Arg, Ala, or Lys; Xaa at position 87 is Leu, Ser, Trp, or Gly; Xaaat position 88 is Ala, Lys, Arg, Val, or Trp; Xaa at position 89 is Thr,Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 90 is Ala,Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 91 is Ala, Pro,Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 92 is Pro, Phe, Arg,Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 93 is Thr, Asp,Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 94 is Arg, Ile, Ser,Glu, Leu, Val, Gln, Lys, His, Ala, or Pro; Xaa at position 95 is His,Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile, orTyr; Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaa atposition 97 is Ile, Val, Lys, Ala, or Asn; Xaa at position 98 is His,Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg,Tyr or Pro; Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln,Gly, Ser, Phe, or His; Xaa at position 100 is Lys, Tyr, Leu, His, Arg,Ile, Ser, Gln, or Pro; Xaa at position 101 is Asp; Xaa at position 102is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 103 is Asp, orSer; Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln,Lys, Ala, Phe, or Gly; Xaa at position 105 is Asn, Pro, Ala, Phe, Ser,Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 106 is Glu,Ser, Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 108 is Arg, Lys,Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro; Xaa at position 109 isArg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 110 is Lys,Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, Ala, or Trp; Xaa atposition 111 is Leu, Ile, Arg, Asp, or Met; Xaa at position 112 is Thr,Val, Gln, Tyr, Glu, His, Ser, or Phe; Xaa at position 113 is Phe, Ser,Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 115 is Leu,Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 116 isLys; Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa atposition 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa atposition 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa atposition 120 is Asn, Ala, Pro, Leu, His, Val, or Gln; Xaa at position121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly; Xaa at position 122 isGln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa atposition 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;wherein fromone to three of the amino acids designated by Xaa are different from thecorresponding amino acids of native (1-133) human interleukin-3; andwherein from 1 to 14 amino acids are optionally deleted from theN-terminus and/or from 1 to 15 amino acids are optionally deleted fromthe C-terminus; and said mutant human interleukin-3 polypeptide has atleast three times greater cell proliferative activity than native humaninterleukin-3 in at least one assay selected from the group consistingof: AML cell proliferation, TF-1 cell proliferation and Methylcelluloseassay; and (b) a polypeptide consisting of an N-terminal methionineresidue, alanine residue or methionine-alanine di-peptide immediatelypreceding said sequence according to (a);(ii) removing hematopoieticcells from said patient; (iii) administering to said patient cancerradiation therapy or chemotherapy; and (iv) returning said hematopoieticcells to said patient.
 64. The method according to claim 63, whereinsaid mutant human interleukin-3 polypeptide has at least ten timesgreater cell proliferative activity than native human interleukin-3. 65.The method according to claim 63, wherein in said mutant humaninterleukin-3 (hIL-3) sequence the amino acids which differ from thecorresponding residue in native human interleukin-3 are selected fromthe group consisting of:position 42 wherein Xaa is Gly, Asp, Ser, Ile,Leu, Met, Tyr, or Ala; position 45 wherein Xaa is Gln, Val, Met or Asn;position 46 wherein Xaa is Asp, Ser, Gln, His or Val; position 50wherein Xaa is Glu or Asp; position 51 wherein Xaa is Asn, Pro or Thr;position 62 wherein Xaa is Asn or Pro; position 76 wherein Xaa is Ser,or Pro; position 82 wherein Xaa is Leu, Trp, Asp, Asn Glu, His, Phe, Seror Tyr; position 95 wherein Xaa is His, Arg, Thr, Asn or Ser; position98 wherein Xaa is His, Ile, Leu, Ala, Gln, Lys, Met, Ser, Tyr or Val;position 100 wherein Xaa is Lys or Arg; position 101 wherein Xaa is Asp;position 105 wherein Xaa is Asn, or Pro; position 108 wherein Xaa isArg, Ala, or Ser; position 116 wherein Xaa is Lys; position 121 whereinXaa is Ala, or Ile; position 122 wherein Xaa is Gln, or Ile; position123 wherein Xaa is Ala, Met or Glu.
 66. The method according to claim65, wherein said mutant human interleukin-3 polypeptide has at least tentimes greater cell proliferative activity than native humaninterleukin-3.
 67. A method of treating a patient consisting of thesteps of:(i) administering to said patient, an amount of a mutant humaninterleukin-3 (IL-3) polypeptide, effective to promote the proliferationand/or differentiation of hematopoietic calls in said patient, whereinsaid mutant human interleukin-3 (hIL-3) polypeptide consists of amodified hIL-3 amino acid sequence selected from the group consistingof: (a) a sequence of(SEQ ID NO:17)wherein; Xaa at position 17 is Ser,Gly, Asp, Met, or Gln; Xaa at position 18 is Asn, His, or Ile; Xaa atposition 19 is Met or Ile; Xaa at position 21 is Asp or Glu; Xaa atposition 23 is Ile, Ala, Leu, or Gly; Xaa at position 24 is Ile, Val, orLeu; Xaa at position 25 is Thr, His, Gln, or Ala; Xaa at position 26 isHis or Ala; Xaa at position 29 is Gln, Asn, or Val; Xaa at position 30is Pro, Gly, or Gln; Xaa at position 31 is Pro, Asp, Gly, or Gln; Xaa atposition 32 is Leu, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 33is Pro or Glu; Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Ala, Arg,Gln, Glu, Ile, Phe, Thr or Met; Xaa at position 35 is Leu, Ala, Asn,Pro, Gln, or Val; Xaa at position 37 is Phe, Ser, Pro, or Trp; Xaa atposition 38 is Asn or Ala; Xaa at position 42 is Gly, Asp, Ser, Cys,Ala, Asn, Ile, Leu, Met, Tyr or Arg; Xaa at position 44 is Asp or Glu;Xaa at position 45 is Gln, Val, Met, Leu, Thr, Ala, Asn, Glu, Ser orLys; Xaa at position 46 is Asp, Phe, Ser, Thr, Ala, Asn, Gln, Glu, His,Ile, Lys, Tyr, Val or Cys; Xaa at position 50 is Glu, Ala, Asn, Ser orAsp; Xaa at position 51 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa atposition 54 is Arg or Ala; Xaa at position 55 is Arg, Thr, Val, Leu, orGly; Xaa at position 56 is Pro, Gly, Ser, Gln, Ala, Arg, Asn, Glu, Leu,Thr, Val or Lys; Xaa at position 60 is Ala or Ser; Xaa at position 62 isAsn, Pro, Thr, or Ile; Xaa at position 63 is Arg or Lys; Xaa at position64 is Ala or Asn; Xaa at position 65 is Val or Thr; Xaa at position 66is Lys or Arg; Xaa at position 67 is Ser, Phe, or His; Xaa at position68 is Leu, Ile, Phe, or His; Xaa at position 69 is Gln, Ala, Pro, Thr,Glu, Arg, or Gly; Xaa at position 71 is Ala, Pro, or Arg; Xaa atposition 72 is Ser, Glu, Arg, or Asp; Xaa at position 73 is Ala or Leu;Xaa at position 76 is Ser, Val, Ala, Asn, Glu, Pro, or Gly; Xaa atposition 77 is Ile or Leu; Xaa at position 79 is Lys, Thr, Gly, Asn,Met, Arg, Ile, or Asp; Xaa at position 80 is Asn, Gly, Glu, or Arg; Xaaat position 82 is Leu, Gln, Trp, Arg, Asp, Ala, Asn, Glu, His, Ile, Met,Phe, Ser, Thr, Tyr or Val; Xaa at position 83 is Pro or Thr; Xaa atposition 85 is Leu or Val; Xaa at position 87 is Leu or Ser; Xaa atposition 88 is Ala or Trp; Xaa at position 91 is Ala or Pro; Xaa atposition 93 is Thr, Asp, Ser, Pro, Ala, Leu, or Arg; Xaa at position 95is His, Pro, Arg, Val, Leu, Gly, Asn, Phe, Ser or Thr; Xaa at position96 is Pro or Tyr; Xaa at position 97 is Ile or Val; Xaa at position 98is His, Ile, Asn, Leu, Ala, Thr, Arg, Gln, Lys, Met, Ser, Tyr, Val orPro; Xaa at position 99 is Ile, Leu, or Val; Xaa at position 100 is Lys,Arg, Ile, Gln, Pro, or Ser; Xaa at position 101 is Asp; Xaa at position104 is Trp or Leu; Xaa at position 105 is Asn, Pro, Ala, Ser, Trp, Gln,Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 106 is Glu or Gly; Xaaat position 108 is Arg, Ala, or Ser; Xaa at position 109 is Arg, Thr,Glu, Leu, or Ser; Xaa at position 112 is Thr, Val, or Gln; Xaa atposition 114 is Tyr or Trp; Xaa at position 115 is Leu or Ala; Xaa atposition 116 is Lys; Xaa at position 117 is Thr or Ser; Xaa at position120 is Asn, Pro, Leu, His, Val, or Gln; Xaa at position 121 is Ala, Ser,Ile, Asn, Pro, Asp, or Gly; Xaa at position 122 is Gln, Ser, Met, Trp,Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa at position 123 is Ala, Met,Glu, His, Ser, Pro, Tyr, or Leu;wherein from one to three of the aminoacids designated by Xaa are different from the corresponding amino acidsof native (1-133) human interleukin-3; and wherein from 1 to 14 aminoacids are optionally deleted from the N-terminus and/or from 1 to 15amino acids are optionally deleted from the C-terminus; and said mutanthuman interleukin-3 polypeptide has at least three times greater cellproliferative activity than native human interleukin-3 in at least oneassay selected from the group consisting of: AML cell proliferation,TF-1 cell proliferation and Methylcellulose assay; and (b) a polypeptideconsisting of an N-terminal methionine residue, alanine residue ormethionine-alanine di-peptide immediately preceding said sequenceaccording to (a);(ii) removing hematopoietic cells from said patient;(iii) administering to said patient cancer radiation therapy orchemotherapy; and (iv) returning said hematopoietic cells to saidpatient.
 68. The method according to claim 67, wherein said mutant humaninterleukin-3 polypeptide has at least ten times greater cellproliferative activity than native human interleukin-3.
 69. A method oftreating a patient consisting of the steps of:(i) administering to saidpatient, an amount of a mutant human interleukin-3 (IL-3) polypeptide,effective to promote the proliferation and/or differentiation ofhematopoietic cells in said patient, wherein said mutant humaninterleukin-3 (hIL-3) polypeptide consists of a modified hIL-3 aminoacid sequence selected from the group consisting of: (a) a sequenceof(SEQ ID NO:19)wherein Xaa at position 3 is Ser, Lys, Gly, Asp, Met,Gln, or Arg; Xaa at position 4 is Asn, His, Leu, Ile, Phe, Arg, or Gln;Xaa at position 5 is Met, Phe, Ile, Arg, Gly, Ala, or Cys; Xaa atposition 6 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala; Xaa at position 7 isAsp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val; Xaa atposition 8 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val, orGly; Xaa at position 9 is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser,or Arg; Xaa at position 10 is Ile, Gly, Val, Arg, Ser, Phe, or Leu; Xaaat position 11 is Thr, His, Gly, Gln, Arg, Pro, or Ala; Xaa at position12 is His, Thr, Phe, Gly, Arg, Ala, or Trp; Xaa at position 13 is Leu,Gly, Arg, Thr, Ser, or Ala; Xaa at position 14 is Lys, Arg, Leu, Gln,Gly, Pro, Val or Trp; Xaa at position 15 is Gln, Asn, Leu, Pro, Arg, orVal; Xaa at position 16 is Pro, His, Thr, Gly, Asp, Gln, Ser, Leu, orLys; Xaa at position 17 is Pro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa atposition 18 is Leu, Val, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa atposition 19 is Pro, Leu, Gln, Ala, Thr, or Glu; Xaa at position 20 isLeu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaaat position 21 is Leu, Ala, Gly, Asn, Pro, Gln, or Val; Xaa at position22 is Asp, Leu, or Val; Xaa at position 23 is Phe, Ser, Pro, Trp, orIle; Xaa at position 24 is Asn, or Ala; Xaa at position 26 is Leu, Trp,or Arg; Xaa at position 27 is Asn, Cys, Arg, Leu, His, Met, Pro; Xaa atposition 28 is Gly, Asp, Ser, Cys, Ala, Lys, Asn, Thr, Leu, Val, Glu,Phe, Tyr, Ile or Met; Xaa at position 29 is Glu, Asn, Tyr, Leu, Phe,Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser; Xaa at position 30 is Asp,Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro; Xaa atposition 31 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Asp, Asn, Arg,Ser, Ala, Ile, Glu, His or Trp; Xaa at position 32 is Asp, Phe, Ser,Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaa atposition 33 is Ile, Gly, Val, Ser, Arg, Pro, or His; Xaa at position 34is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val orAsn; Xaa at position 35 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;Xaa at position 36 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile,Val, His, Phe, Met or Gln; Xaa at position 37 is Asn, Arg, Met, Pro,Ser, Thr, or His; Xaa at position 38 is Asn, His, Arg, Leu, Gly, Ser, orThr; Xaa at position 39 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, orMet; Xaa at position 40 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys,His, Ala or Leu; Xaa at position 41 is Arg, Thr, Val, Ser, Leu, or Gly;Xaa at position 42 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala,Tyr, Phe, Leu, Val or Lys; Xaa at position 43 is Asn or Gly; Xaa atposition 44 is Leu, Ser, Asp, Arg, Gln, Val, or Cys; Xaa at position 45is Glu, Tyr, His, Leu, Pro, or Arg; Xaa at position 46 is Ala, Ser, Pro,Tyr, Asn, or Thr; Xaa at position 47 is Phe, Asn, Glu, Pro, Lys, Arg, orSer; Xaa at position 48 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;Xaa at position 49 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val; Xaa atposition 50 is Ala, Asn, Pro, Ser, or Lys; Xaa at position 51 is Val,Thr, Pro, His, Leu, Phe, or Ser; Xaa at position 52 is Lys, Ile, Arg,Val, Asn, Glu, or Ser; Xaa at position 53 is Ser, Ala, Phe, Val, Gly,Asn, Ile, Pro, or His; Xaa at position 54 is Leu, Val, Trp, Ser, Ile,Phe, Thr, or His; Xaa at position 55 is Gln, Ala, Pro, Thr, Glu, Arg,Trp, Gly, or Leu; Xaa at position 56 is Asn, Leu, Val, Trp, Pro, or Ala;Xaa at position 57 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, orAsn; Xaa at position 58 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;Xaa at position 59 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa atposition 60 is Ile, Met, Thr, Pro, Arg, Gly, Ala; Xaa at position 61 isGlu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu; Xaa at position 62is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp; Xaa at position 63 isIle, Ser, Arg, Thr, or Leu; Xaa at position 64 is Leu, Ala, Ser, Glu,Phe, Gly, or Arg; Xaa at position 65 is Lys, Thr, Gly, Asn, Met, Arg,Ile, or Asp; Xaa at position 66 is Asn, Trp, Val, Gly, Thr, Leu, Glu, orArg; Xaa at position 67 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;Xaa at position 68 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr,Ser, Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 69 is Pro, Ala,Thr, Trp, Arg, or Met; Xaa at position 70 is Cys, Glu, Gly, Arg, Met, orVal; Xaa at position 71 is Leu, Asn, Val, or Gln; Xaa at position 72 isPro, Cys, Arg, Ala, or Lys; Xaa at position 73 is Leu, Ser, Trp, or Gly;Xaa at position 74 is Ala, Lys, Arg, Val, or Trp; Xaa at position 75 isThr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 76 isAla, Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 77 is Ala,Pro, Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 78 is Pro, Phe,Arg, Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 79 is Thr,Asp, Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 80 is Arg, Ile,Ser, Glu, Leu, Val, Gln, Lys, His, Ala or Pro; Xaa at position 81 isHis, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe,Ile or Tyr; Xaa at position 82 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaaat position 83 is Ile, Val, Lys, Ala, or Asn; Xaa at position 84 is His,Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg,Tyr or Pro; Xaa at position 85 is Ile, Leu, Arg, Asp, Val, Pro, Gln,Gly, Ser, Phe, or His; Xaa at position 86 is Lys, Tyr, Leu, His, Arg,Ile, Ser, Gln, or Pro; Xaa at position 87 is Asp; Xaa at position 88 isGly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 89 is Asp, or Ser;Xaa at position 90 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys,Ala, Phe, or Gly; Xaa at position 91 is Asn, Pro, Ala, Phe, Ser, Trp,Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 92 is Glu, Ser,Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 94 is Arg, Lys, Asp,Leu, Thr, Ile, Gln, His, Ser, Ala, or Pro; Xaa at position 95 is Arg,Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 96 is Lys, Asn,Thr, Leu, Gln, Arg, His, Glu, Ser, Ala or Trp; Xaa at position 97 isLeu, Ile, Arg, Asp, or Met; Xaa at position 98 is Thr, Val, Gln, Tyr,Glu, His, Ser, or Phe; Xaa at position 99 is Phe, Ser, Cys, His, Gly,Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position 100 is Tyr,Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 101 is Leu, Asn, Val,Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 102 is Lys; Xaa atposition 103 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa at position104 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa at position 105 isGlu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa at position 106 is Asn,Ala, Pro, Leu, His, Val, or Gln; Xaa at position 107 is Ala, Ser, Ile,Asn, Pro, Lys, Asp, or Gly; Xaa at position 108 is Gln, Ser, Met, Trp,Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa at position 109 is Ala, Met,Glu, His, Ser, Pro, Tyr, or Leu;wherein from one to three of the aminoacids designated by Xaa are different from the corresponding nativeamino acids of (1-133) human interleukin-3; and said mutant humaninterleukin-3 polypeptide has at least three times greater cellproliferative activity than native human interleukin-3 in at least oneassay selected from the group consisting of: AML cell proliferation,TF-1 cell proliferation and Methylcellulose assay; and (b) a polypeptideconsisting of an N-terminal methionine residue, alanine residue ormethionine-alanine di-peptide immediately preceding said sequenceaccording to (a);(ii) removing hematopoietic cells from said patient;(iii) administering to said patient cancer radiation therapy orchemotherapy; and (iv) returning said hematopoietic cells to saidpatient.
 70. The method according to claim 69, wherein said mutant humaninterleukin-3 polypeptide has at least ten times greater cellproliferative activity than native human interleukin-3.
 71. The methodaccording to claim 69, wherein said mutant human interleukin-3polypeptide is selected from the group consisting of:(a) a polypeptidehaving an amino acid sequence of(i) (residues 3-113 of SEQ ID NO:66);(ii) (residues 3-113 of SEQ ID NO:67); (iii) (residues 3-113 of SEQ IDNO:69); or (iv) (SEQ ID NO:218); and (b) an N-terminal methionineresidue, alanine residue or methionine-alanine di-peptide immediatelypreceding said sequence according to (a).
 72. The method according toclaim 71, wherein said mutant human interleukin-3 polypeptide has atleast ten times greater cell proliferative activity than native humaninterleukin-3.
 73. The method according to claim 69, wherein in saidmutant human interleukin-3 (hIL-3) sequence the amino acids which differfrom the corresponding residue in native human interleukin-3 areselected from the group consisting of:position 28 wherein Xaa is Gly,Asp, Ser, Ile, Leu, Met, Tyr, or Ala; position 31 wherein Xaa is Gln,Val, Met or Asn; position 32 wherein Xaa is Asp, Ser, Ala, Gln, His orVal; position 36 wherein Xaa is Glu or Asp; position 37 wherein Xaa isAsn, Pro or Thr; position 48 wherein Xaa is Asn or Pro; position 62wherein Xaa is Ser, or Pro; position 68 wherein Xaa is Leu, Trp, Asp,Asn, Glu, His, Phe, Ser or Tyr; position 81 wherein Xaa is His, Arg,Thr, Asn or Ser; position 84 wherein Xaa is His, Ile, Leu, Ala, Arg,Gln, Lys, Met, Ser, Tyr or Val; position 86 wherein Xaa is Lys or Arg;position 87 wherein Xaa is Asp; position 91 wherein Xaa is Asn, or Pro;position 94 wherein Xaa is Arg, Ala, or Ser; position 102 wherein Xaa isLys; position 107 wherein Xaa is Ala, or Ile; position 108 wherein Xaais Gln, or Ile; position 109 wherein Xaa is Ala, Met or Glu.
 74. Themethod according to claim 73, wherein said mutant human interleukin-3polypeptide has at least ten times greater cell proliferative activitythan native human interleukin-3.
 75. A method of treating a patientconsisting of the steps of:(i) administering to said patient, an amountof a mutant human interleukin-3 (IL-3) polypeptide, effective to promotethe proliferation and/or differentiation of hematopoietic cells in saidpatient, wherein said mutant human interleukin-3 (hIL-3) polypeptideconsists of a modified hIL-3 amino acid sequence selected from the groupconsisting of: (a) a sequence of (SEQ ID NO:21)wherein; Xaa at position3 is Ser, Gly, Asp, Met, or Gln; Xaa at position 4 is Asn, His, or Ile;Xaa at position 5 is Met or Ile; Xaa at position 7 is Asp or Glu; Xaa atposition 9 is Ile, Ala, Leu, or Gly; Xaa at position 10 is Ile, Val, orLeu; Xaa at position 11 is Thr, His, Gln, or Ala; Xaa at position 12 isHis or Ala; Xaa at position 15 is Gln, Asn, or Val; Xaa at position 16is Pro, Gly, or Gln; Xaa at position 17 is Pro, Asp, Gly, or Gln; Xaa atposition 18 is Leu, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 19is Pro or Glu; Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Ala, Arg,Gln, Glu, Ile, Phe, Thr or Met; Xaa at position 21 is Leu, Ala, Asn,Pro, Gln, or Val; Xaa at position 23 is Phe, Ser, Pro, or Trp; Xaa atposition 24 is Asn or Ala; Xaa at position 28 is Gly, Asp, Ser, Cys,Ala, Asn, Ile, Leu, Met Tyr or Arg; Xaa at position 30 is Asp or Glu;Xaa at position 31 is Gln, Val, Met, Leu, Thr, Ala, Asn, Glu, Ser orLys; Xaa at position 32 is Asp, Phe, Ser, Thr, Ala, Asn, Gln, Glu, His,Ile, Lys, Tyr, Val or Cys; Xaa at position 36 is Glu, Ala, Asn, Ser orAsp; Xaa at position 37 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa atposition 40 is Arg or Ala; Xaa at position 41 is Arg, Thr, Val, Leu, orGly; Xaa at position 42 is Pro, Gly, Ser, Gln, Ala, Arg, Asn, Glu, Leu,Thr, Val or Lys; Xaa at position 46 is Ala or Ser; Xaa at position 48 isAsn, Pro, Thr, or Ile; Xaa at position 49 is Arg or Lys; Xaa at position50 is Ala or Asn; Xaa at position 51 is Val or Thr; Xaa at position 52is Lys or Arg; Xaa at position 53 is Ser, Phe, or His; Xaa at position54 is Leu, Ile, Phe, or His; Xaa at position 55 is Gln, Ala, Pro, Thr,Glu, Arg, or Gly; Xaa at position 57 is Ala, Pro, or Arg; Xaa atposition 58 is Ser, Glu, Arg, or Asp; Xaa at position 59 is Ala or Leu;Xaa at position 62 is Ser, Val, Ala, Asn, Glu, Pro, or Gly; Xaa atposition 63 is Ile or Leu; Xaa at position 65 is Lys, Thr, Gly, Asn,Met, Arg, Ile, or Asp; Xaa at position 66 is Asn, Gly, Glu, or Arg; Xaaat position 68 is Leu, Gln, Trp, Arg, Asp, Ala, Asn, Glu, His, Ile, Met,Phe, Ser, Thr, Tyr or Val; Xaa at position 69 is Pro or Thr; Xaa atposition 71 is Leu or Val; Xaa at position 73 is Leu or Ser; Xaa atposition 74 is Ala or Trp; Xaa at position 77 is Ala or Pro; Xaa atposition 79 is Thr, Asp, Ser, Pro, Ala, Leu, or Arg; Xaa at position 81is His, Pro, Arg, Val, Leu, Gly, Asn, Phe, Ser or Thr; Xaa at position82 is Pro or Tyr; Xaa at position 83 is Ile or Val; Xaa at position 84is His, Ile, Asn, Leu, Ala, Thr, Arg, Gln, Lys, Met, Ser, Tyr, Val orPro; Xaa at position 85 is Ile, Leu, or Val; Xaa at position 86 is Lys,Arg, Ile, Gln, Pro, or Ser; Xaa at position 87 is Asp; Xaa at position90 is Trp or Leu; Xaa at position 91 is Asn, Pro, Ala, Ser, Trp, Gln,Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 92 is Glu, or Gly; Xaaat position 94 is Arg, Ala, or Ser; Xaa at position 95 is Arg, Thr, Glu,Leu, or Ser; Xaa at position 98 is Thr, Val, or Gln; Xaa at position 100is Tyr or Trp; Xaa at position 101 is Leu or Ala; Xaa at position 102 isLys; Xaa at position 103 is Thr or Ser; Xaa at position 106 is Asn, Pro,Leu, His, Val, or Gln; Xaa at position 107 is Ala, Ser, Ile, Asn, Pro,Asp, or Gly; Xaa at position 108 is Gln, Ser, Met, Trp, Arg, Phe, Pro,His, Ile, Tyr, or Cys; Xaa at position 109 is Ala, Met, Glu, His, Ser,Pro, Tyr, or Leu;wherein from one to three of the amino acids designatedby Xaa are different from the corresponding amino acids of native(1-133) human interleukin-3; and said mutant human interleukin-3polypeptide has at least three times greater cell proliferative activitythan native human interleukin-3 in at least one assay selected from thegroup consisting of: AML cell proliferation, TF-1 cell proliferation andMethylcellulose assay; and (b) a polypeptide consisting of an N-terminalmethionine residue, alanine residue or methionine-alanine di-peptideimmediately preceding said sequence according to (a);(ii) removinghematopoietic cells from said patient; (iii) administering to saidpatient cancer radiation therapy or chemotherapy; and (iv) returningsaid hematopoietic cells to said patient.
 76. The method according toclaim 75, wherein said mutant human interleukin-3 polypeptide has atleast ten times greater cell proliferative activity than native humaninterleukin-3.
 77. A method of treating a side effect of cancerchemotherapy or radiation therapy in a patient consisting ofadministering to said patient, a therapeutically effective amount of amutant human interleukin-3 (hIL-3) polypeptide consisting of a modifiedhIL-3 amino acid sequence selected from the group consisting of:(a) asequence of (SEQ ID NO:15)wherein; Xaa at position 17 is Ser, Lys, Gly,Asp, Met, Gln, or Arg; Xaa at position 18 is Asn, His, Leu, Ile, Phe,Arg, or Gln; Xaa at position 19 is Met, Phe, Ile, Arg, Gly, Ala, or Cys;Xaa at position 20 is Ile, Cys, Gln, Glu, Arg, Pro, or Ala; Xaa atposition 21 is Asp, Phe, Lys, Arg, Ala, Gly, Glu, Gln, Asn, Thr, Ser orVal; Xaa at position 22 is Glu, Trp, Pro, Ser, Ala, His, Asp, Asn, Gln,Leu, Val or Gly; Xaa at position 23 is Ile, Val, Ala, Leu, Gly, Trp,Lys, Phe, Ser, or Arg; Xaa at position 24 is Ile, Gly, Val, Arg, Ser,Phe, or Leu; Xaa at position 25 is Thr, His, Gly, Gln, Arg, Pro, or Ala;Xaa at position 26 is His, Thr, Phe, Gly, Arg, Ala, or Trp; Xaa atposition 27 is Leu, Gly, Arg, Thr, Ser, or Ala; Xaa at position 28 isLys, Arg, Leu, Gln, Gly, Pro, Val or Trp; Xaa at position 29 is Gln,Asn, Leu, Pro, Arg, or Val; Xaa at position 30 is Pro, His, Thr, Gly,Asp, Gln, Ser, Leu, or Lys; Xaa at position 31 is Pro, Asp, Gly, Ala,Arg, Leu, or Gln; Xaa at position 32 is Leu, Val, Arg, Gln, Asn, Gly,Ala, or Glu; Xaa at position 33 is Pro, Leu, Gln, Ala, Thr, or Glu; Xaaat position 34 is Leu, Val, Gly, Ser, Lys, Glu, Gln, Thr, Arg, Ala, Phe,Ile or Met; Xaa at position 35 is Leu, Ala, Gly, Asn, Pro, Gln, or Val;Xaa at position 36 is Asp, Leu, or Val; Xaa at position 37 is Phe, Ser,Pro, Trp, or Ile; Xaa at position 38 is Asn, or Ala; Xaa at position 40is Leu, Trp, or Arg; Xaa at position 41 is Asn, Cys, Arg, Leu, His, Met,or Pro; Xaa at position 42 is Gly, Asp, Ser, Cys, Asn, Lys, Thr, Leu,Val, Glu, Phe, Tyr, Ile, Met or Ala; Xaa at position 43 is Glu, Asn,Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr, Gly or Ser; Xaa at position44 is Asp, Ser, Leu, Arg, Lys, Thr, Met, Trp, Glu, Asn, Gln, Ala or Pro;Xaa at position 45 is Gln, Pro, Phe, Val, Met, Leu, Thr, Lys, Trp, Asp,Asn, Arg, Ser, Ala, Ile, Glu or His; Xaa at position 46 is Asp, Phe,Ser, Thr, Cys, Glu, Asn, Gln, Lys, His, Ala, Tyr, Ile, Val or Gly; Xaaat position 47 is Ile, Gly, Val, Ser, Arg, Pro, or His; Xaa at position48 is Leu, Ser, Cys, Arg, Ile, His, Phe, Glu, Lys, Thr, Ala, Met, Val orAsn; Xaa at position 49 is Met, Arg, Ala, Gly, Pro, Asn, His, or Asp;Xaa at position 50 is Glu, Leu, Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile,Val, His, Phe, Met or Gln; Xaa at position 51 is Asn, Arg, Met, Pro,Ser, Thr, or His; Xaa at position 52 is Asn, His, Arg, Leu, Gly, Ser, orThr; Xaa at position 53 is Leu, Thr, Ala, Gly, Glu, Pro, Lys, Ser, orMet; Xaa at position 54 is Arg, Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys,His, Ala or Leu; Xaa at position 55 is Arg, Thr, Val, Ser, Leu, or Gly;Xaa at position 56 is Pro, Gly, Cys, Ser, Gln, Glu, Arg, His, Thr, Ala,Tyr, Phe, Leu, Val or Lys; Xaa at position 57 is Asn or Gly; Xaa atposition 58 is Leu, Ser, Asp, Arg, Gln, Val, or Cys; Xaa at position 59is Glu, Tyr, His, Leu, Pro, or Arg; Xaa at position 60 is Ala, Ser, Pro,Tyr, Asn, or Thr; Xaa at position 61 is Phe, Asn, Glu, Pro, Lys, Arg, orSer; Xaa at position 62 is Asn, His, Val, Arg, Pro, Thr, Asp, or Ile;Xaa at position 63 is Arg, Tyr, Trp, Lys, Ser, His, Pro, or Val; Xaa atposition 64 is Ala, Asn, Pro, Ser, or Lys; Xaa at position 65 is Val,Thr, Pro, His, Leu, Phe, or Ser; Xaa at position 66 is Lys, Ile, Arg,Val, Asn, Glu, or Ser; Xaa at position 67 is Ser, Ala, Phe, Val, Gly,Asn, Ile, Pro, or His; Xaa at position 68 is Leu, Val, Trp, Ser, Ile,Phe, Thr, or His; Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg,Trp, Gly, or Leu; Xaa at position 70 is Asn, Leu, Val, Trp, Pro, or Ala;Xaa at position 71 is Ala, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, orAsn; Xaa at position 72 is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp;Xaa at position 73 is Ala, Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa atposition 74 is Ile, Met, Thr, Pro, Arg, Gly, Ala; Xaa at position 75 isGlu, Lys, Gly, Asp, Pro, Trp, Arg, Ser, Gln, or Leu; Xaa at position 76is Ser, Val, Ala, Asn, Trp, Glu, Pro, Gly, or Asp; Xaa at position 77 isIle, Ser, Arg, Thr, or Leu; Xaa at position 78 is Leu, Ala, Ser, Glu,Phe, Gly, or Arg; Xaa at position 79 is Lys, Thr, Asn, Met, Arg, Ile,Gly, or Asp; Xaa at position 80 is Asn, Trp, Val, Gly, Thr, Leu, Glu, orArg; Xaa at position 81 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys;Xaa at position 82 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr,Ser, Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 83 is Pro, Ala,Thr, Trp, Arg, or Met; Xaa at position 84 is Cys, Glu, Gly, Arg, Met, orVal; Xaa at position 85 is Leu, Asn, Val, or Gln; Xaa at position 86 isPro, Cys, Arg, Ala, or Lys; Xaa at position 87 is Leu, Ser, Trp, or Gly;Xaa at position 88 is Ala, Lys, Arg, Val, or Trp; Xaa at position 89 isThr, Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 90 isAla, Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 91 is Ala,Pro, Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 92 is Pro, Phe,Arg, Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 93 is Thr,Asp, Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 94 is Arg, Ile,Ser, Glu, Leu, Val, Gln, Lys, His, Ala, or Pro; Xaa at position 95 isHis, Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe,Ile, or Tyr; Xaa at position 96 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaaat position 97 is Ile, Val, Lys, Ala, or Asn; Xaa at position 98 is His,Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg,Tyr or Pro; Xaa at position 99 is Ile, Leu, Arg, Asp, Val, Pro, Gln,Gly, Ser, Phe, or His; Xaa at position 100 is Lys, Tyr, Leu, His, Arg,Ile, Ser, Gln, or Pro; Xaa at position 101 is Asp; Xaa at position 102is Gly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 103 is Asp, orSer; Xaa at position 104 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln,Lys, Ala, Phe, or Gly; Xaa at position 105 is Asn, Pro, Ala, Phe, Ser,Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 106 is Glu,Ser, Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 108 is Arg, Lys,Asp, Leu, Thr, Ile, Gln, His, Ser, Ala or Pro; Xaa at position 109 isArg, Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 110 is Lys,Ala, Asn, Thr, Leu, Arg, Gln, His, Glu, Ser, Ala, or Trp; Xaa atposition 111 is Leu, Ile, Arg, Asp, or Met; Xaa at position 112 is Thr,Val, Gln, Tyr, Glu, His, Ser, or Phe; Xaa at position 113 is Phe, Ser,Cys, His, Gly, Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position114 is Tyr, Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 115 is Leu,Asn, Val, Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 116 isLys; Xaa at position 117 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa atposition 118 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa atposition 119 is Glu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa atposition 120 is Asn, Ala, Pro, Leu, His, Val, or Gln; Xaa at position121 is Ala, Ser, Ile, Asn, Pro, Lys, Asp, or Gly; Xaa at position 122 isGln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa atposition 123 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;wherein fromone to three of the amino acids designated by Xaa are different from thecorresponding amino acids of native (1-133) human interleukin-3; andwherein from 1 to 14 amino acids are optionally deleted from theN-terminus and/or from 1 to 15 amino acids are optionally deleted fromthe C-terminus; and said mutant human interleukin-3 polypeptide has atleast three times greater cell proliferative activity than native humaninterleukin-3 in at least one assay selected from the group consistingof: AML cell proliferation, TF-1 cell proliferation and Methylcelluloseassay; and (b) a polypeptide consisting of an N-terminal methionineresidue, alanine residue or methionine-alanine di-peptide immediatelypreceding said sequence according to (a).
 78. The method according toclaim 77, wherein said mutant human interleukin-3 polypeptide has atleast ten times greater cell proliferative activity than native humaninterleukin-3.
 79. The method according to claim 77 wherein in saidmutant human interleukin-3 (hIL-3) sequence the amino acids which differfrom the corresponding residue in native human interleukin-3 areselected from the group consisting of:position 42 wherein Xaa is Gly,Asp, Ser, Ile, Leu, Met, Tyr, or Ala; position 45 wherein Xaa is Gln,Val, Met or Asn; position 46 wherein Xaa is Asp, Ser, Gln, His or Val;position 50 wherein Xaa is Glu or Asp; position 51 wherein Xaa is Asn,Pro or Thr; position 62 wherein Xaa is Asn or Pro; position 76 whereinXaa is Ser, or Pro; position 82 wherein Xaa is Leu, Trp, Asp, Asn Glu,His, Phe, Ser or Tyr; position 95 wherein Xaa is His, Arg, Thr, Asn orSer; position 98 wherein Xaa is His, Ile, Leu, Ala, Gln, Lys, Met, Ser,Tyr or Val; position 100 wherein Xaa is Lys or Arg; position 101 whereinXaa is Asp; position 105 wherein Xaa is Asn, or Pro; position 108wherein Xaa is Arg, Ala, or Ser; position 116 wherein Xaa is Lys;position 121 wherein Xaa is Ala, or Ile; position 122 wherein Xaa isGln, or Ile; position 123 wherein Xaa is Ala, Met or Glu.
 80. The methodaccording to claim 79, wherein said mutant human interleukin-3polypeptide has at least ten times greater cell proliferative activitythan native human interleukin-3.
 81. A method of treating a side effectof cancer chemotherapy or radiation therapy in a patient consisting ofadministering to said patient, a therapeutically effective amount of amutant human interleukin-3 (hIL-3) polypeptide consisting of a modifiedhIL-3 amino acid sequence selected from the group consisting of:(a) asequence of (SEQ ID NO:17)wherein; Xaa at position 17 is Ser, Gly, Asp,Met, or Gln; Xaa at position 18 is Asn, His, or Ile; Xaa at position 19is Met or Ile; Xaa at position 21 is Asp or Glu; Xaa at position 23 isIle, Ala, Leu, or Gly; Xaa at position 24 is Ile, Val, or Leu; Xaa atposition 25 is Thr, His, Gln, or Ala; Xaa at position 26 is His or Ala;Xaa at position 29 is Gln, Asn, or Val; Xaa at position 30 is Pro, Gly,or Gln; Xaa at position 31 is Pro, Asp, Gly, or Gln; Xaa at position 32is Leu, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 33 is Pro orGlu; Xaa at position 34 is Leu, Val, Gly, Ser, Lys, Ala, Arg, Gln, Glu,Ile, Phe, Thr or Met; Xaa at position 35 is Leu, Ala, Asn, Pro, Gln, orVal; Xaa at position 37 is Phe, Ser, Pro, or Trp; Xaa at position 38 isAsn or Ala; Xaa at position 42 is Gly, Asp, Ser, Cys, Ala, Asn, Ile,Leu, Met, Tyr or Arg; Xaa at position 44 is Asp or Glu; Xaa at position45 is Gln, Val, Met, Leu, Thr, Ala, Asn, Glu, Ser or Lys; Xaa atposition 46 is Asp, Phe, Ser, Thr, Ala, Asn, Gln, Glu, His, Ile, Lys,Tyr, Val or Cys; Xaa at position 50 is Glu, Ala, Asn, Ser or Asp; Xaa atposition 51 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 54is Arg or Ala; Xaa at position 55 is Arg, Thr, Val, Leu, or Gly; Xaa atposition 56 is Pro, Gly, Ser, Gln, Ala, Arg, Asn, Glu, Leu, Thr, Val orLys; Xaa at position 60 is Ala or Ser; Xaa at position 62 is Asn, Pro,Thr, or Ile; Xaa at position 63 is Arg or Lys; Xaa at position 64 is Alaor Asn; Xaa at position 65 is Val or Thr; Xaa at position 66 is Lys orArg; Xaa at position 67 is Ser, Phe, or His; Xaa at position 68 is Leu,Ile, Phe, or His; Xaa at position 69 is Gln, Ala, Pro, Thr, Glu, Arg, orGly; Xaa at position 71 is Ala, Pro, or Arg; Xaa at position 72 is Ser,Glu, Arg, or Asp; Xaa at position 73 is Ala or Leu; Xaa at position 76is Ser, Val, Ala, Asn, Glu, Pro, or Gly; Xaa at position 77 is Ile orLeu; Xaa at position 79 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp;Xaa at position 80 is Asn, Gly, Glu, or Arg; Xaa at position 82 is Leu,Gln, Trp, Arg, Asp, Ala, Asn, Glu, His, Ile, Met, Phe, Ser, Thr, Tyr orVal; Xaa at position 83 is Pro or Thr; Xaa at position 85 is Leu or Val;Xaa at position 87 is Leu or Ser; Xaa at position 88 is Ala or Trp; Xaaat position 91 is Ala or Pro; Xaa at position 93 is Thr, Asp, Ser, Pro,Ala, Leu, or Arg; Xaa at position 95 is His, Pro, Arg, Val, Leu, Gly,Asn, Phe, Ser or Thr; Xaa at position 96 is Pro or Tyr; Xaa at position97 is Ile or Val; Xaa at position 98 is His, Ile, Asn, Leu, Ala, Thr,Arg, Gln, Lys, Met, Ser, Tyr, Val or Pro; Xaa at position 99 is Ile,Leu, or Val; Xaa at position 100 is Lys, Arg, Ile, Gln, Pro, or Ser; Xaaat position 101 is Asp; Xaa at position 104 is Trp or Leu; Xaa atposition 105 is Asn, Pro, Ala, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp,or His; Xaa at position 106 is Glu or Gly; Xaa at position 108 is Arg,Ala, or Ser; Xaa at position 109 is Arg, Thr, Glu, Leu, or Ser; Xaa atposition 112 is Thr, Val, or Gln; Xaa at position 114 is Tyr or Trp; Xaaat position 115 is Leu or Ala; Xaa at position 116 is Lys; Xaa atposition 117 is Thr or Ser; Xaa at position 120 is Asn, Pro, Leu, His,Val, or Gln; Xaa at position 121 is Ala, Ser, Ile, Asn, Pro, Asp, orGly; Xaa at position 122 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile,Tyr, or Cys; Xaa at position 123 is Ala, Met, Glu, His, Ser, Pro, Tyr,or Leu;wherein from one to three of the amino acids designated by Xaaare different from the corresponding amino acids of native (1-133) humaninterleukin-3; and wherein from 1 to 14 amino acids are optionallydeleted from the N-terminus and/or from 1 to 15 amino acids areoptionally deleted from the C-terminus; and said mutant humaninterleukin-3 polypeptide has at least three times greater cellproliferative activity than native human interleukin-3 in at least oneassay selected from the group consisting of: AML cell proliferation,TF-1 cell proliferation and Methylcellulose assay; and (b) a polypeptideconsisting of an N-terminal methionine residue, alanine residue ormethionine-alanine di-peptide immediately preceding said sequenceaccording to (a).
 82. The method according to claim 81, wherein saidmutant human interleukin-3 polypeptide has at least ten times greatercell proliferative activity than native human interleukin-3.
 83. Amethod of treating a side effect of cancer chemotherapy or radiationtherapy in a patient consisting of administering to said patient, atherapeutically effective amount of a mutant human interleukin-3 (hIL-3)polypeptide consisting of a modified hIL-3 amino acid sequence selectedfrom the group consisting of:(a) a sequence of (SEQ ID NO:19)wherein;Xaa at position 3 is Ser, Lys, Gly, Asp, Met, Gln, or Arg; Xaa atposition 4 is Asn, His, Leu, Ile, Phe, Arg, or Gln; Xaa at position 5 isMet, Phe, Ile, Arg, Gly, Ala, or Cys; Xaa at position 6 is Ile, Cys,Gln, Glu, Arg, Pro, or Ala; Xaa at position 7 is Asp, Phe, Lys, Arg,Ala, Gly, Glu, Gln, Asn, Thr, Ser or Val; Xaa at position 8 is Glu, Trp,Pro, Ser, Ala, His, Asp, Asn, Gln, Leu, Val, or Gly; Xaa at position 9is Ile, Val, Ala, Leu, Gly, Trp, Lys, Phe, Ser, or Arg; Xaa at position10 is Ile, Gly, Val, Arg, Ser, Phe, or Leu; Xaa at position 11 is Thr,His, Gly, Gln, Arg, Pro, or Ala; Xaa at position 12 is His, Thr, Phe,Gly, Arg, Ala, or Trp; Xaa at position 13 is Leu, Gly, Arg, Thr, Ser, orAla; Xaa at position 14 is Lys, Arg, Leu, Gln, Gly, Pro, Val or Trp; Xaaat position 15 is Gln, Asn, Leu, Pro, Arg, or Val; Xaa at position 16 isPro, His, Thr, Gly, Asp, Gln, Ser, Leu, or Lys; Xaa at position 17 isPro, Asp, Gly, Ala, Arg, Leu, or Gln; Xaa at position 18 is Leu, Val,Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 19 is Pro, Leu, Gln,Ala, Thr, or Glu; Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Glu,Gln, Thr, Arg, Ala, Phe, Ile or Met; Xaa at position 21 is Leu, Ala,Gly, Asn, Pro, Gln, or Val; Xaa at position 22 is Asp, Leu, or Val; Xaaat position 23 is Phe, Ser, Pro, Trp, or Ile; Xaa at position 24 is Asn,or Ala; Xaa at position 26 is Leu, Trp, or Arg; Xaa at position 27 isAsn, Cys, Arg, Leu, His, Met, Pro; Xaa at position 28 is Gly, Asp, Ser,Cys, Ala, Lys, Asn, Thr, Leu, Val, Glu, Phe, Tyr, Ile or Met; Xaa atposition 29 is Glu, Asn, Tyr, Leu, Phe, Asp, Ala, Cys, Gln, Arg, Thr,Gly or Ser; Xaa at position 30 is Asp, Ser, Leu, Arg, Lys, Thr, Met,Trp, Glu, Asn, Gln, Ala or Pro; Xaa at position 31 is Gln, Pro, Phe,Val, Met, Leu, Thr, Lys, Asp, Asn, Arg, Ser, Ala, Ile, Glu, His or Trp;Xaa at position 32 is Asp, Phe, Ser, Thr, Cys, Glu, Asn, Gln, Lys, His,Ala, Tyr, Ile, Val or Gly; Xaa at position 33 is Ile, Gly, Val, Ser,Arg, Pro, or His; Xaa at position 34 is Leu, Ser, Cys, Arg, Ile, His,Phe, Glu, Lys, Thr, Ala, Met, Val or Asn; Xaa at position 35 is Met,Arg, Ala, Gly, Pro, Asn, His, or Asp; Xaa at position 36 is Glu, Leu,Thr, Asp, Tyr, Lys, Asn, Ser, Ala, Ile, Val, His, Phe, Met or Gln; Xaaat position 37 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position38 is Asn, His, Arg, Leu, Gly, Ser, or Thr; Xaa at position 39 is Leu,Thr, Ala, Gly, Glu, Pro, Lys, Ser, or Met; Xaa at position 40 is Arg,Asp, Ile, Ser, Val, Thr, Gln, Asn, Lys, His, Ala or Leu; Xaa at position41 is Arg, Thr, Val, Ser, Leu, or Gly; Xaa at position 42 is Pro, Gly,Cys, Ser, Gln, Glu, Arg, His, Thr, Ala, Tyr, Phe, Leu, Val or Lys; Xaaat position 43 is Asn or Gly; Xaa at position 44 is Leu, Ser, Asp, Arg,Gln, Val, or Cys; Xaa at position 45 is Glu, Tyr, His, Leu, Pro, or Arg;Xaa at position 46 is Ala, Ser, Pro, Tyr, Asn, or Thr; Xaa at position47 is Phe, Asn, Glu, Pro, Lys, Arg, or Ser; Xaa at position 48 is Asn,His, Val, Arg, Pro, Thr, Asp, or Ile; Xaa at position 49 is Arg, Tyr,Trp, Lys, Ser, His, Pro, or Val; Xaa at position 50 is Ala, Asn, Pro,Ser, or Lys; Xaa at position 51 is Val, Thr, Pro, His, Leu, Phe, or Ser;Xaa at position 52 is Lys, Ile, Arg, Val, Asn, Glu, or Ser; Xaa atposition 53 is Ser, Ala, Phe, Val, Gly, Asn, Ile, Pro, or His; Xaa atposition 54 is Leu, Val, Trp, Ser, Ile, Phe, Thr, or His; Xaa atposition 55 is Gln, Ala, Pro, Thr, Glu, Arg, Trp, Gly, or Leu; Xaa atposition 56 is Asn, Leu, Val, Trp, Pro, or Ala; Xaa at position 57 isAla, Met, Leu, Pro, Arg, Glu, Thr, Gln, Trp, or Asn; Xaa at position 58is Ser, Glu, Met, Ala, His, Asn, Arg, or Asp; Xaa at position 59 is Ala,Glu, Asp, Leu, Ser, Gly, Thr, or Arg; Xaa at position 60 is Ile, Met,Thr, Pro, Arg, Gly, Ala; Xaa at position 61 is Glu, Lys, Gly, Asp, Pro,Trp, Arg, Ser, Gln, or Leu; Xaa at position 62 is Ser, Val, Ala, Asn,Trp, Glu, Pro, Gly, or Asp; Xaa at position 63 is Ile, Ser, Arg, Thr, orLeu; Xaa at position 64 is Leu, Ala, Ser, Glu, Phe, Gly, or Arg; Xaa atposition 65 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp; Xaa atposition 66 is Asn, Trp, Val, Gly, Thr, Leu, Glu, or Arg; Xaa atposition 67 is Leu, Gln, Gly, Ala, Trp, Arg, Val, or Lys; Xaa atposition 68 is Leu, Gln, Lys, Trp, Arg, Asp, Glu, Asn, His, Thr, Ser,Ala, Tyr, Phe, Ile, Met or Val; Xaa at position 69 is Pro, Ala, Thr,Trp, Arg, or Met; Xaa at position 70 is Cys, Glu, Gly, Arg, Met, or Val;Xaa at position 71 is Leu, Asn, Val, or Gln; Xaa at position 72 is Pro,Cys, Arg, Ala, or Lys; Xaa at position 73 is Leu, Ser, Trp, or Gly; Xaaat position 74 is Ala, Lys, Arg, Val, or Trp; Xaa at position 75 is Thr,Asp, Cys, Leu, Val, Glu, His, Asn, or Ser; Xaa at position 76 is Ala,Pro, Ser, Thr, Gly, Asp, Ile, or Met; Xaa at position 77 is Ala, Pro,Ser, Thr, Phe, Leu, Asp, or His; Xaa at position 78 is Pro, Phe, Arg,Ser, Lys, His, Ala, Gly, Ile or Leu; Xaa at position 79 is Thr, Asp,Ser, Asn, Pro, Ala, Leu, or Arg; Xaa at position 80 is Arg, Ile, Ser,Glu, Leu, Val, Gln, Lys, His, Ala or Pro; Xaa at position 81 is His,Gln, Pro, Arg, Val, Leu, Gly, Thr, Asn, Lys, Ser, Ala, Trp, Phe, Ile orTyr; Xaa at position 82 is Pro, Lys, Tyr, Gly, Ile, or Thr; Xaa atposition 83 is Ile, Val, Lys, Ala, or Asn; Xaa at position 84 is His,Ile, Asn, Leu, Asp, Ala, Thr, Glu, Gln, Ser, Phe, Met, Val, Lys, Arg,Tyr or Pro; Xaa at position 85 is Ile, Leu, Arg, Asp, Val, Pro, Gln,Gly, Ser, Phe, or His; Xaa at position 86 is Lys, Tyr, Leu, His, Arg,Ile, Ser, Gln, or Pro; Xaa at position 87 is Asp; Xaa at position 88 isGly, Leu, Glu, Lys, Ser, Tyr, or Pro; Xaa at position 89 is Asp, or Ser;Xaa at position 90 is Trp, Val, Cys, Tyr, Thr, Met, Pro, Leu, Gln, Lys,Ala, Phe, or Gly; Xaa at position 91 is Asn, Pro, Ala, Phe, Ser, Trp,Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaa at position 92 is Glu, Ser,Ala, Lys, Thr, Ile, Gly, or Pro; Xaa at position 94 is Arg, Lys, Asp,Leu, Thr, Ile, Gln, His, Ser, Ala, or Pro; Xaa at position 95 is Arg,Thr, Pro, Glu, Tyr, Leu, Ser, or Gly; Xaa at position 96 is Lys, Asn,Thr, Leu, Gln, Arg, His, Glu, Ser, Ala or Trp; Xaa at position 97 isLeu, Ile, Arg, Asp, or Met; Xaa at position 98 is Thr, Val, Gln, Tyr,Glu, His, Ser, or Phe; Xaa at position 99 is Phe, Ser, Cys, His, Gly,Trp, Tyr, Asp, Lys, Leu, Ile, Val or Asn; Xaa at position 100 is Tyr,Cys, His, Ser, Trp, Arg, or Leu; Xaa at position 101 is Leu, Asn, Val,Pro, Arg, Ala, His, Thr, Trp, or Met; Xaa at position 102 is Lys; Xaa atposition 103 is Thr, Ser, Asn, Ile, Trp, Lys, or Pro; Xaa at position104 is Leu, Ser, Pro, Ala, Glu, Cys, Asp, or Tyr; Xaa at position 105 isGlu, Ser, Lys, Pro, Leu, Thr, Tyr, or Arg; Xaa at position 106 is Asn,Ala, Pro, Leu, His, Val, or Gln; Xaa at position 107 is Ala, Ser, Ile,Asn, Pro, Lys, Asp, or Gly; Xaa at position 108 is Gln, Ser, Met, Trp,Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa at position 109 is Ala, Met,Glu, His, Ser, Pro, Tyr, or Leu;wherein from one to three of the aminoacids designated by Xaa are different from the corresponding nativeamino acids of (1-133) human interleukin-3; and said mutant humaninterleukin-3 polypeptide has at least three times greater cellproliferative activity than native human interleukin-3 in at least oneassay selected from the group consisting of: AML cell proliferation,TF-1 cell proliferation and Methylcellulose assay; and (b) a polypeptideconsisting of an N-terminal methionine residue, alanine residue ormethionine-alanine di-peptide immediately preceding said sequenceaccording to (a).
 84. The method according to claim 83, wherein saidmutant human interleukin-3 polypeptide has at least ten times greatercell proliferative activity than native human interleukin-3.
 85. Themethod according to claim 83, wherein said mutant human interleukin-3polypeptide is selected from the group consisting of:(a) a polypeptidehaving an amino acid sequence of(i) (residues 3-113 of SEQ ID NO:66);(ii) (residues 3-113 of SEQ ID NO:67); (iii) (residues 3-113 of SEQ IDNO:69); or (iv) (SEQ ID NO:218); and (b) an N-terminal methionineresidue, alanine residue or methionine-alanine di-peptide immediatelypreceding said sequence according to (a).
 86. The method according toclaim 85, wherein said mutant human interleukin-3 polypeptide has atleast ten times greater cell proliferative activity than native humaninterleukin-3.
 87. The method according to claim 83, wherein in saidmutant human interleukin-3 (hIL-3) sequence the amino acids which differfrom the corresponding residue in native human interleukin-3 areselected from the group consisting of:position 28 wherein Xaa is Gly,Asp, Ser, Ile, Leu, Met, Tyr, or Ala; position 31 wherein Xaa is Gln,Val, Met or Asn; position 32 wherein Xaa is Asp, Ser, Ala, Gln, His orVal; position 36 wherein Xaa is Glu or Asp; position 37 wherein Xaa isAsn, Pro or Thr; position 48 wherein Xaa is Asn or Pro; position 62wherein Xaa is Ser, or Pro; position 68 wherein Xaa is Leu, Trp, Asp,Asn, Glu, His, Phe, Ser or Tyr; position 81 wherein Xaa is His, Arg,Thr, Asn or Ser; position 84 wherein Xaa is His, Ile, Leu, Ala, Arg,Gln, Lys, Met, Ser, Tyr or Val; position 86 wherein Xaa is Lys or Arg;position 87 wherein Xaa is Asp; position 91 wherein Xaa is Asn, or Pro;position 94 wherein Xaa is Arg, Ala, or Ser; position 102 wherein Xaa isLys; position 107 wherein Xaa is Ala, or Ile; position 108 wherein Xaais Gln, or Ile; position 109 wherein Xaa is Ala, Met or Glu.
 88. Themethod according to claim 87, wherein said mutant human interleukin-3polypeptide has at least ten times greater cell proliferative activitythan native human interleukin-3.
 89. A method of treating a side effectof cancer chemotherapy or radiation therapy in a patient consisting ofadministering to said patient, a therapeutically effective amount of amutant human interleukin-3 (hIL-3) polypeptide consisting of a modifiedhIL-3 amino acid sequence selected from the group consisting of:(a) asequence of (SEQ ID NO:21)wherein; Xaa at position 3 is Ser, Gly, Asp,Met, or Gln; Xaa at position 4 is Asn, His, or Ile; Xaa at position 5 isMet or Ile; Xaa at position 7 is Asp or Glu; Xaa at position 9 is Ile,Ala, Leu, or Gly; Xaa at position 10 is Ile, Val, or Leu; Xaa atposition 11 is Thr, His, Gln, or Ala; Xaa at position 12 is His or Ala;Xaa at position 15 is Gln, Asn, or Val; Xaa at position 16 is Pro, Gly,or Gln; Xaa at position 17 is Pro, Asp, Gly, or Gln; Xaa at position 18is Leu, Arg, Gln, Asn, Gly, Ala, or Glu; Xaa at position 19 is Pro orGlu; Xaa at position 20 is Leu, Val, Gly, Ser, Lys, Ala, Arg, Gln, Glu,Ile, Phe, Thr or Met; Xaa at position 21 is Leu, Ala, Asn, Pro, Gln, orVal; Xaa at position 23 is Phe, Ser, Pro, or Trp; Xaa at position 24 isAsn or Ala; Xaa at position 28 is Gly, Asp, Ser, Cys, Ala, Asn, Ile,Leu, Met Tyr or Arg; Xaa at position 30 is Asp or Glu; Xaa at position31 is Gln, Val, Met, Leu, Thr, Ala, Asn, Glu, Ser or Lys; Xaa atposition 32 is Asp, Phe, Ser, Thr, Ala, Asn, Gln, Glu, His, Ile, Lys,Tyr, Val or Cys; Xaa at position 36 is Glu, Ala, Asn, Ser or Asp; Xaa atposition 37 is Asn, Arg, Met, Pro, Ser, Thr, or His; Xaa at position 40is Arg or Ala; Xaa at position 41 is Arg, Thr, Val, Leu, or Gly; Xaa atposition 42 is Pro, Gly, Ser, Gln, Ala, Arg, Asn, Glu, Leu, Thr, Val orLys; Xaa at position 46 is Ala or Ser; Xaa at position 48 is Asn, Pro,Thr, or Ile; Xaa at position 49 is Arg or Lys; Xaa at position 50 is Alaor Asn; Xaa at position 51 is Val or Thr; Xaa at position 52 is Lys orArg; Xaa at position 53 is Ser, Phe, or His; Xaa at position 54 is Leu,Ile, Phe, or His; Xaa at position 55 is Gln, Ala, Pro, Thr, Glu, Arg, orGly; Xaa at position 57 is Ala, Pro, or Arg; Xaa at position 58 is Ser,Glu, Arg, or Asp; Xaa at position 59 is Ala or Leu; Xaa at position 62is Ser, Val, Ala, Asn, Glu, Pro, or Gly; Xaa at position 63 is Ile orLeu; Xaa at position 65 is Lys, Thr, Gly, Asn, Met, Arg, Ile, or Asp;Xaa at position 66 is Asn, Gly, Glu, or Arg; Xaa at position 68 is Leu,Gln, Trp, Arg, Asp, Ala, Asn, Glu, His, Ile, Met, Phe, Ser, Thr, Tyr orVal; Xaa at position 69 is Pro or Thr; Xaa at position 71 is Leu or Val;Xaa at position 73 is Leu or Ser; Xaa at position 74 is Ala or Trp; Xaaat position 77 is Ala or Pro; Xaa at position 79 is Thr, Asp, Ser, Pro,Ala, Leu, or Arg; Xaa at position 81 is His, Pro, Arg, Val, Leu, Gly,Asn, Phe, Ser or Thr; Xaa at position 82 is Pro or Tyr; Xaa at position83 is Ile or Val; Xaa at position 84 is His, Ile, Asn, Leu, Ala, Thr,Arg, Gln, Lys, Met, Ser, Tyr, Val or Pro; Xaa at position 85 is Ile,Leu, or Val; Xaa at position 86 is Lys, Arg, Ile, Gln, Pro, or Ser; Xaaat position 87 is Asp; Xaa at position 90 is Trp or Leu; Xaa at position91 is Asn, Pro, Ala, Ser, Trp, Gln, Tyr, Leu, Lys, Ile, Asp, or His; Xaaat position 92 is Glu, or Gly; Xaa at position 94 is Arg, Ala, or Ser;Xaa at position 95 is Arg, Thr, Glu, Leu, or Ser; Xaa at position 98 isThr, Val, or Gln; Xaa at position 100 is Tyr or Trp; Xaa at position 101is Leu or Ala; Xaa at position 102 is Lys; Xaa at position 103 is Thr orSer; Xaa at position 106 is Asn, Pro, Leu, His, Val, or Gln; Xaa atposition 107 is Ala, Ser, Ile, Asn, Pro, Asp, or Gly; Xaa at position108 is Gln, Ser, Met, Trp, Arg, Phe, Pro, His, Ile, Tyr, or Cys; Xaa atposition 109 is Ala, Met, Glu, His, Ser, Pro, Tyr, or Leu;wherein fromone to three of the amino acids designated by Xaa are different from thecorresponding amino acids of native (1-133) human interleukin-3; andsaid mutant human interleukin-3 polypeptide has at least three timesgreater cell proliferative activity than native human interleukin-3 inat least one assay selected from the group consisting of: AML cellproliferation, TF-1 cell proliferation and Methylcellulose assay; and(b) a polypeptide consisting of an N-terminal methionine residue,alanine residue or methionine-alanine di-peptide immediately precedingsaid sequence according to (a).
 90. The method according to claim 89,wherein said mutant human interleukin-3 polypeptide has at least tentimes greater cell proliferative activity than native humaninterleukin-3.